WO2013004116A1 - C-3 substituted-9-deoxidized-9a-aza-9a-erythromycin a derivative - Google Patents

C-3 substituted-9-deoxidized-9a-aza-9a-erythromycin a derivative Download PDF

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Publication number
WO2013004116A1
WO2013004116A1 PCT/CN2012/076470 CN2012076470W WO2013004116A1 WO 2013004116 A1 WO2013004116 A1 WO 2013004116A1 CN 2012076470 W CN2012076470 W CN 2012076470W WO 2013004116 A1 WO2013004116 A1 WO 2013004116A1
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Prior art keywords
methyl
ethyl
dimethylamino
oxy
hetero
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PCT/CN2012/076470
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French (fr)
Chinese (zh)
Inventor
刘兴金
张许科
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洛阳惠中兽药有限公司
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Publication of WO2013004116A1 publication Critical patent/WO2013004116A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis

Definitions

  • the present invention is in the field of medical technology and relates to novel C-3 substituted -9-deoxy-9A-aza-9A-homoerythromycin A derivatives, processes for their preparation and pharmaceutical compositions of the compounds.
  • the invention further relates to the use of the derivative for the manufacture of a medicament for the treatment and/or prevention of bacterial infections, protozoal infections.
  • Macrolides are an important class of anti-infectives. Since the discovery of erythromycin in 1952, after 60 years of development, it has become the second largest class of ⁇ -lactam antibiotics in clinical applications. Anti-infective drugs have made a huge contribution to the treatment of human and animal diseases.
  • the invention provides a
  • R 2 is a hydroxyl group
  • R 3 is a hetero atom-substituted or unsubstituted organic substance, and the hetero atom is one or more of halogen, N, 0 and S Species; is 11, benzyloxycarbonyl, benzoyl or acetyl.
  • R 2 o is an organic or inorganic group containing at least one of C, H, 0, N, S and halogen. More preferably, R 3 is -CH 2 NHR 3 o, wherein R 3 o is an organic or inorganic group containing at least one of C, H, 0, N, S and halogen.
  • R 3 o is preferably selected from the group consisting of H, amino, methyl, ethyl, allyl, n-butyl, isobutyl, 2-methoxyethyl, cyclopentyl, 3-methoxypropyl, 3-ethoxypropyl, n-propyl, isopropyl, 2-hydroxyethyl, cyclopropyl, 2,2,2-trifluoroethyl, 2-propynyl, sec-butyl, tert-butyl, Orthodecyl, vinyl, ethynyl, 1-methyl-1-propenyl, 3-methoxypropynyl, 3-dimethylamino-1-propynyl, 3-hydroxy-1-propanyl Block group, 3-hydroxy-1-propenyl, 3-hydroxypropyl, 3-methoxy-1-propenyl, 3-methoxypropyl, 1-propynyl, azidomethyl, A Acylmethyl, 6-cyan
  • R 3 is -CH 2 NH-(CH 2 ) m R4o, wherein m is an integer from 1 to 4, and 0 is at least C, H, 0, N, S and halogen An atomic organic or inorganic group. More preferably, R40 is selected from H, an organic group with or without a hetero atom, and the hetero atom is halogen, N, 0 or 8.
  • 0 is preferably selected from -C20 fluorenyl group, dC 6 decyloxy group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, and 5-20 with or without a hetero atom.
  • a aryl or heteroaryl group, and the aforementioned group may be optionally bonded to a carbon-containing substituent.
  • 0 is a C 6 -C 1Q aryl group having a substituent or a C 5 -C 2Q heteroaryl group, and the hetero atom in the heteroaryl group is halogen, N, 0 or 8.
  • R 3 is -CH 2 SR 5Q , wherein R 5 () is an organic substance substituted or unsubstituted with a hetero atom which is halogen, N, 0 or S.
  • R 5Q is selected from the group consisting of d- o fluorenyl with or without a hetero atom, dC 6 decyloxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and 5-20 aryl Or a heteroaryl group, and the aforementioned group may be optionally bonded to a carbon-containing substituent group.
  • R 5 o is methyl, ethyl, allyl, n-butyl, isobutyl, 2-methoxyethyl, cyclopentyl, 3-methoxypropyl , 3-ethoxypropyl, n-propyl, isopropyl, 2-hydroxyethyl, cyclopropyl, sec-butyl, tert-butyl, or n-hexyl.
  • hydroxyl group is 11.
  • the compound of formula (I) of the invention is specifically:
  • 111) (21, 33, 41, 5, 811, 1011, 111, 128, 138, 141)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Xylose]oxy]-2-ethyl-13- ⁇ [(furan-2-yl-methyl)-amino]-methyl ⁇ -3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
  • the present invention also provides the use of the above compound or a pharmaceutically acceptable salt thereof for the preparation of a medicament for treating a bacterial infection or a protozoal infection of a mammal, fish or bird; or the compound of the present invention for synthesizing other macrolide antibiotics The use of intermediates.
  • the invention also provides a composition comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • the starting compound 1 can be prepared or commercially available according to synthetic methods well known to those skilled in the art, including the synthetic methods described in U.S. Patent 4,474,768 and U.S. Patent 4,517,359.
  • the C-2' hydroxyl group in the compound 1 can be selectively protected by treating the compound 1 with an equivalent amount of acetic anhydride in methylene chloride in the absence of an external base, wherein R4 is an acetyl group. a compound of formula II.
  • the acetyl protecting group can be removed by treating the compound of formula II with methanol at 23 ⁇ 65'C for 10 to 48 hours.
  • the hydroxyl group of C-2' can also be protected using other hydroxy protecting groups well known to those skilled in the art, such as benzyloxycarbonyl (Cbz), during which the hydroxyl group of C-4" is also protected, but does not affect subsequent experiments.
  • 'Hydroxyl can be protected by treatment with a benzyl chloroformate in tetrahydrofuran and water in a compound of formula II using Cbz selectivity in one step.
  • the Cbz group can be removed using conventional catalytic hydrogenation, or it can be used in a suitable manner as is well known in the art.
  • the organic solvent can be removed by reacting for 2 to 5 days in a temperature range of about room temperature to about 100 ° C.
  • the hydroxyl groups of C-2' and C-4" are considered by those skilled in the art. The proper form is protected or deprotected.
  • step b SP: For the removal of the C-3 claratin sugar, the de-sugaring compound of the formula III is obtained by removing it with hydrochloric acid in ethanol/water using a removal method well known to those skilled in the art.
  • the hydroxyl group of C-3 of the formula III is oxidized.
  • the synthesis focus on the mother nucleus concentrates on the oxidation of the hydroxyl group at the C-3 position.
  • the C-3 hydroxyl group of formula III is oxidized to the corresponding ketone by methods well known to those skilled in the art, including one or more of the methods described in Jcrnmal of Anti-biotics, 1988, pages 1029-1047.
  • a ketone of formula IV can be prepared using dimethyl sulfoxide and a suitable activator.
  • the reaction conditions conventionally used for oxidation include: a) Corey-kim oxidation: J. Med.
  • the oxidation method in step c is preferably dimethyl sulfoxide and trifluoroacetic anhydride and triethylamine for oxidation.
  • the protected defatted material is dissolved in a suitable solvent: dichloromethyl hydrazine, acetone, ethyl acetate, isopropyl acetate
  • the ester or the like is preferably dichloromethane, and then trifluoroacetic anhydride is added, preferably dropwise, and the reaction is carried out for 0 to 3 hours.
  • Triethylamine is added dropwise, and the reaction is carried out for 0 to 3 hours.
  • step c using 1-ethyl-(3-dimethylaminopropyl)carbonyldiimide hydrochloride/dimethylsulfoxide in dichloromethane with a compound of formula III, stirring, cooling To -15 ° C ⁇ 25 ° C, preferably 0 ° C, adding trifluoroacetic acid pyridinium chloride
  • the hydrocarbon generation solution has a controlled temperature of 3'C or less, and the reaction is completed to obtain the oxide of the general formula IV.
  • step d the compound of the formula 3b can be obtained in two ways.
  • a sodium base such as sodium hydride
  • a solvent such as tetrahydrofuran, an ether solvent
  • hydrazine hydrazine-dimethyl
  • the compound of the formula V can be obtained by treating the compound of the formula IV in a temperature range of from 0 Torr to about 60 ° C in a carboxamide, or dimethyl sulfoxide, or a mixture of two or more of the foregoing solvents.
  • the compound of the formula V can be converted into an organic substance in which R 2 is a hydroxyl group and R 3 is a hetero atom substituted or unsubstituted, and the hetero atom is one of halogen, N, 0 and S or More specifically; R 3 is -CH 2 R 20 , wherein R 2 o is an organic or inorganic group containing at least one of C, H, 0, N, S and halogen.
  • the formula HR 2Q can be used as a starting material, in a solvent having or without polarity such as water, methanol, tetrahydrofuran, or a mixture thereof, at about room temperature to about In the temperature range of 100 ° C, preferably 60 ⁇ , any treatment in the presence of a reagent such as potassium iodide, magnesium perchlorate, lithium tetrafluoroborate, pyridine hydrochloride or tetradecyl halogenated hinge halogenating reagent such as tetrabutylammonium bromide
  • a reagent such as potassium iodide, magnesium perchlorate, lithium tetrafluoroborate, pyridine hydrochloride or tetradecyl halogenated hinge halogenating reagent such as tetrabutylammonium bromide
  • a compound of the formula V gives a compound of the formula (I). The process is especially useful when R 3 is -CH 2 NHR
  • the general formula HSR 5 o can be used as a starting material, in the presence or absence of a polar solvent such as water, methanol, tetrahydrofuran, or a mixture thereof, at about room temperature to about In the temperature range of 100'C, preferably 60'C, in the presence of a reagent such as potassium iodide, magnesium perchlorate, lithium tetrafluoroborate, pyridine hydrochloride or tetradecyl ammonium halide halogenating reagent such as tetrabutylammonium bromide
  • a reagent such as potassium iodide, magnesium perchlorate, lithium tetrafluoroborate, pyridine hydrochloride or tetradecyl ammonium halide halogenating reagent such as tetrabutylammonium bromide
  • the compound of the formula V is treated to give a compound of the formula (I) a C-3-substitute
  • halogen in the present invention includes, unless otherwise stated, fluorine, chlorine, bromine or iodine.
  • mercapto in the present invention includes, unless otherwise stated, saturated monovalent hydrocarbon residues having a linear, cyclic or branched chain or a mixture thereof. It will be understood that when referring to the cyclic moiety, there are at least 3 carbon atoms in the hydrocarbyl group. Such cyclic moieties include, for example, cyclopropyl, cyclobutyl and cyclopentyl.
  • alkoxy in the present invention, unless otherwise specified, includes -0-alkyl, wherein alkyl is as defined above.
  • aryl in the present invention includes, unless otherwise stated, an organic residue derived from an aromatic hydrocarbon by removal of a hydrogen such as a phenyl group or a naphthyl group.
  • 5*20-membered heteroaryl in the present invention includes, unless otherwise stated, an aromatic heterocyclic group containing one or more hetero atoms each selected from 0, S and N, wherein each heterocyclic group It has 5-20 atoms in the ring system.
  • suitable 5-20 membered heteroaryl groups include pyridinyl, furyl, thienyl, pyrazolyl, (1,2,3)- and (1,2,4)-triazolyl, pyrazine
  • the compounds of the invention may contain asymmetric carbon atoms and thus exist in different enantiomeric and diastereomeric forms.
  • the mixture of diastereomers can be separated into individual diastereomers according to their respective physicochemical differences using methods known in the art, for example, by chromatography or fractional crystallization. Conversion of the enantiomeric mixture to a mixture of diastereomers by reaction with a suitable optically active compound (eg, an alcohol), followed by separation of the diastereomers and conversion (eg, hydrolysis) of the individual diastereomers affords the corresponding pure Enantiomer.
  • a suitable optically active compound eg, an alcohol
  • conversion eg, hydrolysis
  • Treatment includes the use of a composition of the invention to treat or prevent a bacterial infection or a protozoal infection.
  • Bacterial infection and “protozoal infection” as used herein, unless otherwise indicated, include bacterial infections and protozoal infections that occur in mammals, birds, fish, and can be administered by the use of antibiotics such as the compounds of the invention. Treatment and prevention of bacterial infections and diseases of protozoal infections.
  • the bacterial infections and protozoal infections of the present invention and human diseases caused by diseases of these infections include: by pathogenic streptococci, Haemophilus influenzae, Moraxella, Staphylococcus aureus, Legionella, Actinobacilli, mycoplasma, chlamydia, pneumonia, bronchitis, otitis media, sinusitis, tonsillitis, pharyngitis, nephritis; fever, skin and soft tissue infections caused by pathogenic staphylococci, streptococci, coryneform bacteria, Abscess, osteomyelitis; urinary tract disease caused by pathogenic staphylococcus, enterococci, chlamydia, spirochete, mycoplasma, Neisseria infection, cervicitis, gonorrhea infection, sexually transmitted diseases, etc.; Lyme disease caused by spirochete infection; conjunctivitis caused by Chlamydia trachomati
  • the bacterial infections and protozoal infections of the animals which can be treated and prevented according to the invention and diseases involving these infections include the following diseases: from the hemolytic Pasteurella, Pasteurella multocida, M. bovis, or Bo Bovine respiratory diseases caused by Deuterium infection; bovine intestinal diseases caused by infection with Escherichia coli or protozoa (such as coccidia); by Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, lactation Cow mastitis caused by Streptococcus, Klebsiella, Corynebacterium, Enterococcus infection; Bovine and swine metritis caused by E.
  • protozoal diseases caused by protozoa such
  • the therapeutic dose of the effective dose of the present invention is 2-50 mg/kg, preferably 10 mg/kg, in a single administration.
  • the "pharmaceutically acceptable salts" of the present invention include, unless otherwise stated, salts of acids or bases which may be present in the compounds of the invention.
  • the compounds of the invention which are basic in nature can form salts with various inorganic or organic acids.
  • a pharmaceutically acceptable acid useful in the preparation of a basic compound of the invention including inorganic or organic acids, such as formate, acetate, propionate, lactate, citrate, tartrate, Oxalate, malate, hydrochloride, sulphate, nitrate, bisulfate, phosphate, acid salt, nicotinate, salicylate, pantothenate, ascorbate, succinate , maleate, gentisate, fumarate, gluconate, gluconate, sucrose, benzoate, glutamate, methanesulfonate, ethanesulfonate, Toluenesulfonate, p-toluenesulfonate and various amino acids.
  • the pharmaceutical composition for treating a mammalian, avian or fish bacterial infection or a protozoan infection of the present invention comprises a compound containing the general formula (I) or a pharmaceutically acceptable salt as an active ingredient, and a pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carrier means any diluent or adjuvant which can be used in the pharmaceutical field.
  • the pharmaceutical composition of the present invention is in the form of an oral preparation, an injection, or an external preparation.
  • the oral preparation of the present invention is a powder, a tablet, a capsule, a granule, a solution, a suspension.
  • the injection is a powder injection, an emulsion, a coagulant, a solution; the external preparation is an ointment, a drop.
  • the carrier in the pharmaceutical composition of the present invention refers to an auxiliary component necessary for the formulation of the pharmaceutical composition, and includes: a diluent, a solubilizer, an antioxidant, a flavoring agent, a preservative, an excipient, and a coagulating agent.
  • the examples provided below illustrate specific embodiments of the invention, but the invention is not limited to the scope of the following examples.
  • the derivative nuclear magnetic resonance spectrum was measured by Bruker ARX-400, and the mass spectrum was determined by LCQ Series LC/MS.
  • the high performance liquid phase was detected by Waters ultra performance liquid chromatography (UPLC) ACQUITY.
  • the raw materials and reagents used were labeled with the main reagents and The rest of the batch numbers are commercially available analytically pure or chemically pure.
  • the solvent ratios used in the silica gel column and thin layer chromatography are all volume ratios as understood by those skilled in the art unless otherwise stated.
  • the purpose of this example is to prepare a compound of the above formula 3, which is named: (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-2-ethyl-3, 4, 10 ,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-2-0- [( Phenylmethoxy)-hetero]- ⁇ -hexyranopyranosyl]oxy]oxyx-6-azacyclopentadecane-15-one.
  • Example 8 The "n-butylamine (0.395 mL, 0.2938, 4 mmoL)" in Example 8 was changed to use "3,4,5-trimethoxy-benzylamine (0.395 mL)", and the rest was the same as in Example 8. 0.08 g of the title compound was obtained.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use "benzylamine 5 mL", and the rest was the same as in Example 14. A crude product of 0.28 g was obtained in the middle to give the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use “tetrahydropyrrole 5 mL", and the rest was the same as in Example 14. Intermediate was obtained in 0.25 g of crude product to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "aniline 5 mL", and the rest was the same as in Example 14. A crude product of 0.30 g was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "1-methoxypropylamine 5 mL", and the residue obtained in the same manner as in Example 14 was obtained.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use "n-hexylamine 5 mL", and the rest was the same as in Example 14. 0.33 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-ethoxypropanamine 5 mL", and the residue was obtained in the same manner as in Example 14 to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “diethylamine 5 mL", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use "N-methyl-n-butylamine 5 mL", and the rest was the same as in Example 14. 0.23 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “N-methyl-n-propylamine 5 mL", and the rest was the same as in Example 14. 0.2 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use “ethylamine 5 mL", and the rest was the same as in Example 14. 0.2 g of crude product was obtained in the middle to give the title compound.
  • Replacement page (Article 26) TLC RfN).51 (dichloroformamidine: methanol 7:1)
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "N-methylethylamine 5 mL", and the rest was the same as in Example 14. 0.29 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “2-trifluoroethylamine 5 mL", and the rest was the same as in Example 14. In the middle, 0.28 g of crude product was obtained, which gave the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "1-hydroxyethylamine 5 mL", and the rest was the same as in Example 14. In the middle, 0.27 g of crude product was obtained, which gave the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “dimethylamine 5 mL", and the rest was the same as in Example 14. 0.25 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use “imidazole 4g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL” in Example 14 was changed to use "bis(2-hydroxyethyl)amine 4g", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use “pyrrole 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use "N-methyl-1-hydroxyethylamine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "1,2,3-triazole 4g", and the rest was the same as in Example 14. In the middle, 0.28 g of crude product was obtained, which gave the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “2-propargylamine 4 mL", and the rest was the same as in Example 14. 0.27 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-methylimidazole 4g", and the rest was the same as in Example 14. In the middle, 0.29 g of crude product was obtained, which gave the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use “divinylamine 4 mL", and the rest was the same as in Example 14. In the middle, 0.28 g of crude product was obtained, which gave the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use “diethanolamine 4 mL", and the rest was the same as in Example 14. In the middle, 0,23 g of crude product was obtained, and the title compound was finally obtained.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "methylamine 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “isopropylamine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “3-methylbutylamine 4 mL", and the rest was the same as in Example 14. In the middle, 0.24 g of crude product was obtained, which gave the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use “cycloethylamine 4 mL", and the rest was the same as in Example 14. 0.23 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “diethylamine 4 mL", and the rest was the same as in Example 14. 0.21 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use “cyclopentylamine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use “p-methoxybenzylamine 4 mL", and the rest was the same as in Example 14. 0.23 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "sodium hydrogencarbonate 2.0 g and p-nitrobenzylamine hydrochloride 4.0 g", and the rest was the same as in Example 14. 0.23 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use “p-chlorobenzylamine 4 mL", and the rest was the same as in Example 14. Intermediate was obtained in 0.25 g of crude product to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3,4-difluorobenzylamine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use “p-methylaminopyridine 4g", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2,6-difluorobenzylamine 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use “p-fluorobenzylamine 4 mL", and the rest was the same as in Example 14. Intermediate was obtained in 0.25 g of crude product to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “3-fluorobenzylamine 4 mL", and the rest was the same as in Example 14. 0.25 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use “o-fluorobenzylamine 4 mL", and the rest was the same as in Example 14. Intermediate was obtained in 0.25 g of crude product to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use "2,4-difluorobenzylamine 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use "2,5-difluorobenzylamine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3,5-difluorobenzylamine 4 mL", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "4.0 g of NaHC0 3 and 1-(4-fluorophenyl)piperazine hydrochloride 4.0 g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “o-trifluoromethylbenzylamine 4 mL", and the rest was the same as in Example 14. 0.27 g of crude product was obtained in the middle to give the title compound.
  • Example 60 Replacement Page (Rule 26) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3-trifluoromethyl-benzyl-amino)methyl]-l l-[[3, 4,6-trideoxy - 3 - (dimethylamino) - ⁇ -D- xylopyranosyl hexyl] oxy] -2-ethyl-3,5-tetrahydroxy--3,4,10,13- , 8,10,12,14-hexamethyloxy-hetero-6-nitrohecyclopentadecane-15-one (see below for structural formula)
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “m-trifluoromethylbenzylamine 4 mL", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "sodium hydrogencarbonate 2.0 g and N-(2-fluorophenyl)ethylamine hydrochloride 4.0 g", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
  • Example 26 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "sodium hydrogencarbonate 2.0 g and N-(3-fluorophenyl)ethylamine hydrochloride 4.0 g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-fluoro-6-trifluoromethylbenzylamine 4.0g", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-(N-methylamino)pyridine 4.0g", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "4-hydroxy-3-methoxy-benzylamine 4.0 mL", and the rest was the same as Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use “pepperamine 4 mL", and the rest was the same as in Example 14. 0.27 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use 3-methoxybenzylamine 4 mL", and the remainder was the same as in Example 14. 0.25 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-methoxybenzylamine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-aminopyridine 4.0g", and the rest was the same as in Example 14. In the middle, 0.24 g of crude product was obtained, which gave the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “2-methoxyethylamine 4 mL", and the rest was the same as in Example 14.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use "2-hydroxy-N-methylethylamine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-methyl-aminopyridine 4.0g", and the rest was the same as in Example 14. 0.21 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to "hydroxylamine 4.0 g", and the rest was the same as in Example 14. Get a replacement page in the middle (Article 26) 0.21 g of crude product, the title compound was obtained.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-hydroxyethylamine 4 mL", and the rest was the same as in Example 14. A 0.20 g crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-fluoro-N-methylaniline 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 26 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-amino-6-chloropyridine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use "4-hydroxy-n-butylamine 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “4-aminomethylbenzoic acid 4.0 g", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use "2-allylamine 4 mL", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-amino-1,4,4-trimethyl-cyclohexyl-methylamine 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use "2-(2-hydroxy)ethylaminoethylamine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "sodium hydrogencarbonate 3.0 g and 2-chloro-4-methoxybenzylamine hydrochloride 4.0 g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "1-methyl-3-phenylpropylamine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use “piperazine 4g", and the rest was the same as in Example 14. 0.21 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use "4-methylaminopyridine 4g", and the residue obtained in the same manner as in Example 14 was obtained to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "4-methylamino-3-chloropyridine 4g", and the rest was the same as in Example 14. 0.21 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use “trifluoroacetamide 4g", and the rest was the same as in Example 14. In the middle, 0.24 g of crude product was obtained, which gave the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "4-methylamino-6-chloropyridine 4g", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use “n-pentylamine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
  • Example 26 The "t-butylamine 4.5 mL" in Example 14 was changed to use “1H-benzo-2-aminoimidazole 4g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 "4.5 mL of tert-butylamine” to use " ⁇ , ⁇ '- dimethyl - 4 mL hydrazine", to obtain 0.23 g of crude product remaining with the intermediate of Example 14, to give the final title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “2,6-difluoro-4-methoxybenzylamine 4 mL", and the rest was the same as Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “diethylene glycolamine 4 mL", and the rest was the same as in Example 14. A 0.20 g crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-chloroethylamine hydrochloride 4.0 g", and the residue obtained in the same manner as in Example 14 was obtained.
  • Example 14 The “tert-butylamine 4.5 mL” in Example 14 was changed to use "2-aminobutyric acid 4.0g", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use " ⁇ -aminopropionic acid amine 4.0g", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-nitro-4-fluoroaniline 4g", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-fluoro-4-bromoaniline 4g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-amino-5-bromo-pyrimidine 4g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use "3,5-bistrifluoromethylaniline 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "t-butylamine 4.5 mL" in Example 14 was changed to use “N-methylaminomorpholine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3,4-diaminopyridine 4g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2,4-dimethylaniline 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
  • Example 14 The "tert-butylamine 4.5 mL" in Example 14 was changed to use “3-chloroaniline 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.

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Abstract

The present invention relates to a compound as represented by general formula (I) and a pharmaceutically acceptable salt thereof, wherein R1 is H, hydroxyl or methoxyl; R2 is hydroxyl; R3 is heteroatom-substituted or unsubstituted organic matter, and the heteroatom is one or more of halogens, N, O and S; R4 is H, carbobenzoxy, benzoyl or acetyl. The compound of the present invention as represented by the general formula (I) is an antibacterial agent, and can be used for the treatment of various bacteria and protozoan infections. The present invention also relates to a use of the compound, a preparation method thereof and a composition formed therewith.

Description

C-3取代的 -9-脱氧 -9A-氮杂 -9A-高红霉素 A衍生物  C-3 substituted -9-deoxy-9A-aza-9A-homoerythromycin A derivative
技术领域 Technical field
本发明属于医药技术领域， 涉及新的 C-3取代的 -9-脱氧 -9A-氮杂 -9A-高红霉素 A衍 生物， 它们的制备方法以及所述化合物的药物组合物。 本发明还涉及该衍生物用于制备 治疗和 /或预防细菌感染、 原生动物感染类疾病药物中的用途。  The present invention is in the field of medical technology and relates to novel C-3 substituted -9-deoxy-9A-aza-9A-homoerythromycin A derivatives, processes for their preparation and pharmaceutical compositions of the compounds. The invention further relates to the use of the derivative for the manufacture of a medicament for the treatment and/or prevention of bacterial infections, protozoal infections.
背景技术 Background technique
大环内酯类药物是一类重要的抗感染药物， 自从 1952年红霉素发现至今， 经过 60 年的发展， 在临床应用中已成为仅次于 β-内酰胺类抗生素的第二大类抗感染药物， 为人 和动物疾病的治疗做出了巨大的贡献。  Macrolides are an important class of anti-infectives. Since the discovery of erythromycin in 1952, after 60 years of development, it has become the second largest class of β-lactam antibiotics in clinical applications. Anti-infective drugs have made a huge contribution to the treatment of human and animal diseases.
但是大环内酯类抗生素的发展面临许多难题， 至今， 没有一个大环内酯类抗生素能 够很好地抑制临床分离的高水平组成性 MLSB耐药的金黄色葡萄球菌、 化脓链球菌， 而 且细菌的耐药性将由大环内酯向酮内酯渗透， 多重耐药问题不可避免。 这就需要寻找新 的高活性实体， 研制新型的抑制耐药菌， 无诱导耐药的抗生素。 However, the development of macrolide antibiotics faces many challenges. To date, no macrolide antibiotics have been able to inhibit clinically isolated high levels of constitutive MLS B resistant Staphylococcus aureus, Streptococcus pyogenes, and Bacterial resistance will be infiltrated by macrolides to ketolides, and multi-drug resistance is inevitable. This requires finding new high-activity entities, developing new antibiotic-resistant bacteria, and antibiotic-inducing antibiotics.
发明内容 Summary of the invention
本发明提供一种具有  The invention provides a
Figure imgf000002_0001
其中， 1^是11， 羟基或甲氧基； R2是羟基； R3是以杂原子取代或未取代的有机物， 且所述杂原子为卤素、 N、 0和 S中的一种或多种； 是 11、 苄氧羰基、 苯甲酰基或乙 酰基。
Figure imgf000002_0001
Wherein 1 is 11 or a hydroxy group or a methoxy group; R 2 is a hydroxyl group; R 3 is a hetero atom-substituted or unsubstituted organic substance, and the hetero atom is one or more of halogen, N, 0 and S Species; is 11, benzyloxycarbonyl, benzoyl or acetyl.
根据本发明， 优选 为 -C¾R2o, 其中 R2o为含 C、 H、 0、 N、 S和卤素中至少一种 原子的有机或无机基团。 其中， 更优选的是， R3为 -CH2NHR3o， 其中 R3o为含 C、 H、 0、 N、 S和卤素中至少一种原子的有机或无机基团。 在本发明中， R3o优选自 H， 氨基， 甲 基， 乙基， 烯丙基， 正丁基， 异丁基， 2-甲氧乙基， 环戊基， 3-甲氧丙基， 3-乙氧丙基， 正丙基， 异丙基， 2-羟基乙基， 环丙基， 2，2,2-三氟乙基， 2-丙炔基， 仲丁基， 叔丁基， 正已基， 乙烯基， 乙炔基， 1-甲基 -1-丙烯基， 3-甲氧基小丙炔基， 3-二甲基氨基 -1-丙炔 基， 3-羟基 -1-丙块基， 3-羟基 -1-丙烯基， 3-羟丙基， 3-甲氧基 -1-丙烯基， 3-甲氧基丙基， 1-丙炔基， 叠氮基甲基， 甲酰基甲基， 6-氰基 -1-戊炔基， 3-二甲基氨基 -1-丙烯基， 或 3- 替换页 （细则第 26条) 二甲基氨基丙基。 2 According to the invention, preference is given to -C3⁄4R 2 o, wherein R 2 o is an organic or inorganic group containing at least one of C, H, 0, N, S and halogen. More preferably, R 3 is -CH 2 NHR 3 o, wherein R 3 o is an organic or inorganic group containing at least one of C, H, 0, N, S and halogen. In the present invention, R 3 o is preferably selected from the group consisting of H, amino, methyl, ethyl, allyl, n-butyl, isobutyl, 2-methoxyethyl, cyclopentyl, 3-methoxypropyl, 3-ethoxypropyl, n-propyl, isopropyl, 2-hydroxyethyl, cyclopropyl, 2,2,2-trifluoroethyl, 2-propynyl, sec-butyl, tert-butyl, Orthodecyl, vinyl, ethynyl, 1-methyl-1-propenyl, 3-methoxypropynyl, 3-dimethylamino-1-propynyl, 3-hydroxy-1-propanyl Block group, 3-hydroxy-1-propenyl, 3-hydroxypropyl, 3-methoxy-1-propenyl, 3-methoxypropyl, 1-propynyl, azidomethyl, A Acylmethyl, 6-cyano-1-pentynyl, 3-dimethylamino-1-propenyl, or 3-substituted page (Rule 26) Dimethylaminopropyl. 2
在本发明的另一个实施方案中， R3为 -CH2NH-(CH2)mR4o， 其中 m是 1-4的整数， 0 为含 C、 H、 0、 N、 S 和卤素中至少一种原子的有机或无机基团。 其中， 更优选的是， R40选自 H， 含有或不含有杂原子的有机基团， 所述杂原子为卤素、 N、 0或8。 In another embodiment of the invention, R 3 is -CH 2 NH-(CH 2 ) m R4o, wherein m is an integer from 1 to 4, and 0 is at least C, H, 0, N, S and halogen An atomic organic or inorganic group. More preferably, R40 is selected from H, an organic group with or without a hetero atom, and the hetero atom is halogen, N, 0 or 8.
在本发明上述技术方案中， 0优选自含有或不含有杂原子的 -C20垸基， d-C6垸 氧基， C2-C6链烯基， C2-C6炔基， 和 5-20元芳基或杂芳基， 且前述基团可任选地连接有 含碳的取代基团。更为优选的是， 0为含有或不含有取代基的 C6-C1Q芳基或 C5-C2Q的杂 芳基， 所述杂芳基中杂原子为卤素、 N、 0或8。 In the above technical solution of the present invention, 0 is preferably selected from -C20 fluorenyl group, dC 6 decyloxy group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, and 5-20 with or without a hetero atom. A aryl or heteroaryl group, and the aforementioned group may be optionally bonded to a carbon-containing substituent. More preferably, 0 is a C 6 -C 1Q aryl group having a substituent or a C 5 -C 2Q heteroaryl group, and the hetero atom in the heteroaryl group is halogen, N, 0 or 8.
根据本发明的又一个实施例， R3为 -CH2SR5Q, 其中 R5()为以杂原子取代或未取代的 有机物，所述杂原子为卤素、 N、0或 S。优选其中 R5Q为选自含有或不含有杂原子的 d- o 垸基， d-C6垸氧基， C2-C6链烯基， C2-C6炔基， 和 5-20元芳基或杂芳基， 且前述基团 可任选地连接有含碳的取代基团。 根据本发明， 更为优选的是， 其中 R5o为甲基， 乙基， 烯丙基， 正丁基， 异丁基， 2-甲氧乙基， 环戊基， 3-甲氧丙基， 3-乙氧丙基， 正丙基， 异 丙基， 2-羟基乙基， 环丙基， 仲丁基， 叔丁基， 或正己基。 According to still another embodiment of the present invention, R 3 is -CH 2 SR 5Q , wherein R 5 () is an organic substance substituted or unsubstituted with a hetero atom which is halogen, N, 0 or S. Preferably wherein R 5Q is selected from the group consisting of d- o fluorenyl with or without a hetero atom, dC 6 decyloxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and 5-20 aryl Or a heteroaryl group, and the aforementioned group may be optionally bonded to a carbon-containing substituent group. More preferably, according to the invention, wherein R 5 o is methyl, ethyl, allyl, n-butyl, isobutyl, 2-methoxyethyl, cyclopentyl, 3-methoxypropyl , 3-ethoxypropyl, n-propyl, isopropyl, 2-hydroxyethyl, cyclopropyl, sec-butyl, tert-butyl, or n-hexyl.
另外， 在本发明中， 优选所述 是羟基， 是11。  Further, in the present invention, it is preferred that the hydroxyl group is 11.
优选地， 本发明的通式（I )化合物具体地是：  Preferably, the compound of formula (I) of the invention is specifically:
1) (2R，3S，4R,5R，8R，10R，11R，12S，13S,14R)-13- [(正丙氨基）甲基] -1 1- { [3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基 ] } -2-乙基 -3，4，10，13-四羟基 -3，5,8，10，12,14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  1) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13- [(n-propylamino)methyl] -1 1- { [3,4,6-tripleoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy] }-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
2) (21 ,38，411，51，811,101，1111，128，138,141 )-13-[(环丙基氨基）甲基]-11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5,8，10,12,14- 六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 2) (21, 38, 411, 51, 811, 101, 1111, 128, 138, 141)-13-[(cyclopropylamino)methyl]-11-[[3,4,6-trideoxy-3- (two Methylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,1 4 - Methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
3) (21 ,33，41，51 ,81，101 ,1 11 ,128,133,1411)-13-[(正丁基氨基）甲基]-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12,14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  3) (21, 33, 41, 51, 81, 101, 1 11 , 128, 133, 1411)-13-[(n-butylamino)methyl]-11-[[3,4,6-trideoxy-3 - (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 - hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
4) (2R,3S,4R,5R,8R,10R,1 lR，12S，13S，14R)-U-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃 木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -13-((2-羟基 -3-甲基-苄胺基)甲基) -3，5，8,10，12,14- 六甲基 -1-氧-杂 -6-氮杂环十五浣 -15-酮  4) (2R, 3S, 4R, 5R, 8R, 10R, 1 lR, 12S, 13S, 14R)-U-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-((2-hydroxy-3-methyl-benzylamino)methyl)-3 ,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
5) (211，38，411，51 ,811，101，111，128，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-3-0-己吡喃 木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10，12,14-六甲基 -13-((3,4,5-三甲氧基 -苄基 胺)甲基) -1-氧-杂 -6-氮杂环十五垸 -15-酮；  5) (211, 38, 411, 51, 811, 101, 111, 128, 138, 141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-((3,4 ,5-trimethoxy-benzylamine)methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
6) (2 ,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(2-甲氧基乙基-氨基）甲基] -11-[[3,4,6- 三脱氧 -3- (二甲基氨基） -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  6) (2,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(2-methoxyethyl-amino)methyl] -11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
7) (211,33，41，51 ,81 ,101 ,1 11，128，135,141 )-13-[(哌啶基）甲基]-11-[[3,4，6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5，8,10,12,14-六甲基 小氧-杂 -6-氮杂环十五垸 -15-酮；  7) (211,33,41,51,81,101,1 11,128,135,141 )-13-[(piperidinyl)methyl]-11-[[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
替换页 （细则第 26条） ) (211,33,41，51，811,101 ,111 ,128，138,141 )-13-[(吗啉基）甲基]-11-[[3，4，6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 小氧-杂 -6-氮杂环十五烷 -15-酮；Replacement page (Article 26) ) (211, 33, 41, 51, 811, 101, 111, 128, 138, 141)-13-[(morpholinyl)methyl]-11-[[3,4,6-trideoxy-3-(dimethyl) Amino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl Oxy-hetero-6-azacyclopentadecane-15-one;
) (2 33,411，51 ,81 ,101 ,1 11 ,128,138，141 )-13-[(叔丁基氨基）甲基]-11-[[3,4，6-三脱氧 (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5,8,10，12,14- 六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；(2 33,411,51 ,81 ,101 ,1 11 ,128,138,141 )-13-[(tert-butylamino)methyl]-11-[[3,4,6-trideoxy(dimethylamino) -β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy- Hetero-6-azacyclopentadecane-15-one;
0) (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(苄基氨基）甲基 ]-11-[[3,4,6-三脱氧0) (2R, 3S, 4R, 5R, 8R, 10R, 1 lR, 12S, 13S, 14R)-13-[(benzylamino)methyl]-11-[[3,4,6-trideoxy
-3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5，8，10，12，14- 六甲基 -1-氧-杂 -6_氮杂环十五垸—15 -酮；-3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero- 6 -nitrozacyclopentadecane- 15 -one;
1) (2R,3S，4R,5R，8R，10R，11R，12S,13S,14R)-13- [(环戊氨基）甲基] -11-[[3,4,6-三脱氧1) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13- [(cyclopentylamino)methyl] -11-[[3,4,6-trideoxy
-3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10，12，14- 六甲基 -1-氧-杂 _6·氮杂环十五垸 _15_酮；-3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero- 6 , nitrogen heterocycle, fifteen fluorene, 15 ketone;
) (211,38,411,51 ,81，101，111 ,128,138,1411)-13-[(苯氨基）甲基] -11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8，10，12，14- 六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； ) (211, 38, 411, 51, 81, 101, 111, 128, 138, 1411)-13-[(phenylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethylamino) -β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1 - oxo-hetero-6-azacyclopentadecane-15-one;
) (21，38，411，51，81，101 ,111，123,138，1411)-13-[(1-甲氧基丙氨基）甲基]-11-[[3，4，6-三 脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10,13-四羟基 -3,5,8,10,12，14-六甲基 -1-氧杂 -6-氮杂环十五垸 -15-酮； ) (21, 38, 411, 51, 81, 101, 111, 123, 138, 1411)-13-[(1-methoxypropylamino)methyl]-11-[[3,4,6-trideoxy- 3-(Dimethylamino)-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyl-1-oxa-6-azacyclopentadecane-15-one;
) (2R,3S，4R，5R,8R,10R，11R,12S，13S，14R)-13- [(正己氨基）甲基] -11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5,8,10,12,14- 六甲基 -1-氧杂 -6-氮杂环十五垸 -15-酮； ) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13- [(n-hexylamino)methyl] -11-[[3,4,6-trideoxy-3- ( Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Methyl-1-oxa-6-azacyclopentadecane-15-one;
) (2 33，411,51，811,101 ,1111,123,133,1411)-13-[(2-乙氧基丙氨基）甲基]-11-[[3，4,6-三脱 氧 -3-(二甲基氨基）-β-0-己吡喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 -3,5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； ) (2 33,411,51,811,101 ,1111,123,133,1411)-13-[(2-ethoxypropylamino)methyl]-11-[[3,4,6-trideoxy-3-( Dimethylamino)-β-0-hexyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-six Methyl small oxygen-hetero-6-azacyclopentadecane-15-one;
) (2 ,38，4! ,51，81，101，111，128,133,141 )-13-[(二乙氨基）甲基]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12,14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； ) (2,38,4!,51,81,101,111,128,133,141 )-13-[(diethylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethyl) -amino-)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl -1-oxo-hetero-6-azacyclopentadecane-15-one;
) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[( N-甲基丁氨基）甲基] -1 1-[[3,4，6-三脱 氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； ) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(N-methylbutylamino)methyl] -1 1-[[3,4,6- Trideoxy-3-(dimethylamino)-PD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
) (2 ,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[( N-甲基丙氨基）甲基] -1 1-[[3，4,6-三脱 氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3,5,8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； ) (2,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(N-methylpropylamino)methyl] -1 1-[[3,4,6- Trideoxy-3-(dimethylamino)-PD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(乙基氨基）甲基 ]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12,14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； ) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(ethylamino)methyl]-11-[[3,4,6-trideoxy-3 - (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 - hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
) (21 ,38,41，51，81 ,1011,111 ,128,133,141 )-13-[( 甲基乙氨基）甲基]-11-[[3,4,6-三脱  ) (21,38,41,51,81,1011,111,128,133,141 )-13-[(methylethylamino)methyl]-11-[[3,4,6-tride
3 3
替换页 （细则第 26条) Κ,Τ/C 2012/ ϋ / Ο ^ ι 氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 - 3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) Κ,Τ/C 2012/ ϋ / Ο ^ ι Oxy-3-(dimethylamino)-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra Hydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
21) (2 ，33,41，51 ,81 ,1011，111 ,128，138,141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基）-卩-0-己  21) (2,33,41,51,81,1011,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl
吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12，14-六甲基 -13-[(2,2，2-三氟乙 氨基)甲基] -1 -氧-杂 -6-氮杂环十五垸 -15-酮；  Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(2,2, 2-trifluoroethylamino)methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
22) (21138，4 51，81 ,101，111 ,128，133,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃  22) (21138,4 51,81,101,111,128,133,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexanpyran
木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12，14-六甲基 -13-[(3-硝基苄基氨基）甲 基] -1-氧-杂 -6-氮杂环十五垸 -15-酮  Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(3-nitrobenzyl) Amino)methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one
23) (21，38，4!，51，81，101，111，123，133，141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)^-0-己  23) (21,38,4!,51,81,101,111,123,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)^-0- already
吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -13-[(1-羟基 -乙基氨基） -甲 基] -3,5,8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(1-hydroxy-ethylamino)-methyl]-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
24) (21，38，4!，5 ,81，1011，111 ,128,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)^-0-己  24) (21,38,4!,5,81,1011,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)^-0-hexyl
吡喃木糖基]氧基] -13- [(二甲基氨基)甲基] -2-乙基 -3，4，10,13-四羟基 -3,5，8,10,12，14- 六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  Pyranopyranyl]oxy]-13-[(dimethylamino)methyl]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 - hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
25) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13S, 14R)- 11 -[[3，4,6-三脱氧 -3- (二甲基氨基）-p-D-己 25) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13S, 14R)- 11 -[[3,4,6-Trideoxy-3-(dimethylamino)-pD -already
吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -13- [(咪唑基）甲基] -3,5，8，10,12，14-六甲 基- 1-氧-杂 -6-氮杂环十五垸 -15-酮；  Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(imidazolyl)methyl] -3,5,8,10,12,14-six Methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
26) (21 ,38,41 ,51，81，101，111 ,128，138，1411)-13-[(双(2-羟乙基）氨基）甲基]-1卜[[3,4,6-三  26) (21, 38, 41, 51, 81, 101, 111, 128, 138, 1411)-13-[(bis(2-hydroxyethyl)amino)methyl]-1 b [[3,4, 6-three
脱氧 -3-(二甲基氨基 )-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  Deoxy-3-(dimethylamino)-β-indole-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
27) (2! ,38，41 ,51，81，101 ,1111，128，133，141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基）^-0-己  27) (2!, 38, 41, 51, 81, 101, 1111, 128, 133, 141)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)^-0 -already
吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四轻基 -3，5,8，10，12,14-六甲基 -13- [(吡咯）甲 基] -1-氧-杂 -6-氮杂环十五垸 -15-酮；  Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrakily-3,5,8,10,12,14-hexamethyl-13-[(pyrrole) -1-oxo-hetero-6-azacyclopentadecane-15-one;
28) (2 38，411，51，811，101，1111，128,133，141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基）-卩-0-己  28) (2 38,411,51,811,101,1111,128,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl
吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-{[(1-羟基-乙基) -甲基 -氨] -甲 基}-3,5，8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-{[(1-hydroxy-ethyl)-methyl-amino]-methyl}-3 , 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
29) (2 ，38,411,51，811,1011，1111,128,135，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己  29) (2,38,411,51,811,1011,1111,128,135,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl
吡喃木糖基]氧基] -2-乙基 -3,4，10,13-四羟基 -3，5,8,10，12,14-六甲基 -13-{ [1,2,3]三氮 唑基小甲基 }小氧-杂 -6-氮杂环十五垸 -15-酮；  Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{ [1,2, 3] triazolyl small methyl} small oxygen-hetero-6-azacyclopentadecane-15-one;
30) (2 ，38,411，51 ,81，101 ,111 ,128,133,141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基）-卩-0-己 30) (2,38,411,51,81,101,111,128,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl
吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5，8，10,12，14-六甲基 -13- [(炔丙基)氨基 甲基] -1-氧-杂 -6-氮杂环十五垸 -15-酮；  Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(propargyl) Aminomethyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
31) (211，38，41，51，81，101，1 11，128，138,141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基）- -0-己  31) (211,38,41,51,81,101,1 11,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)- -0-hexyl
吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5,8,10，12，14-六甲基 -13-(2-甲基 -咪唑 -1-基-甲基)小氧-杂 -6-氮杂环十五垸 -15-酮；  Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(2-methyl- Imidazolyl-1-yl-methyl)oxy-hetero-6-azetidine-decaquinone-15-one;
32) (211，33,411,51 ,81 ,101 ,1 111,123,133,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基)- -0-己  32) (211,33,411,51,81,101,1 111,123,133,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)- -0-hexyl
吡喃木糖基]氧基] -2-氧 -13- (二乙烯基氨基甲基） -2-乙基 -3,4，10，13-四羟基  Pyranopyranyl]oxy]-2-oxo-13-(divinylaminomethyl)-2-ethyl-3,4,10,13-tetrahydroxy
4  4
替换页 （细则第 26条) -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
33) (211，38，41 ,51 ,81，101 ,111 ,123,133,1411)-1 1 -[[3,4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-[(2-羟基 -1-羟基 -甲基 -乙基氨基) -甲 基] -3,5，8，10,12,14-六甲基 -1 -氧-杂 -6-氮杂环十五垸 -15-酮； 33) (211,38,41,51,81,101,111,123,133,1411)-1 1 -[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(2-hydroxy-1-hydroxy-methyl-ethylamino)-methyl] - 3,5,8,10,12,14-hexamethyl-1 -oxo-hetero-6-azacyclopentadecane-15-one;
34) (21，38,41，51，81，101，1 11，128,138，141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5,8,10,12，14-六甲基 -13- [(甲氨基）甲 基] -1-氧-杂 -6-氮杂环十五垸 -15-酮； 34) (21,38,41,51,81,101,1 11,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(methylamino) Methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
35) (21 ,38,4! ,511,81 ,101，111 ,128,138,141 )-1 1 -[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13- (异丙氨基-甲基) -3,5,8,10,12,14-六甲 基 -1 -氧-杂 -6-氮杂环十五烷 -15-酮； 35) (21,38,4!,511,81,101,111,128,138,141)-1 1 -[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexidyl Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(isopropylamino-methyl)-3,5,8,10,12,14-hexa -1 -oxy-hetero-6-azacyclopentadecane-15-one;
36) (2R,3S,4R,5R,8R, 10R,11R,12S,13S,14R)-11-[[3 ,4,6-三脱氧 -3- (二甲基氨基 )-p-D-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12，14-六甲基 -13-[(3-甲基 -丁基 氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮；  36) (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-pD-hexid Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(3-methyl- Butylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
37) (2尺，38,4!，511,81，1011，1 11，128，133,141 )-13-[(>^-杂环丙垸基）甲基]-11-[[3,4,6-三脱 氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3,4，10，13-四羟基 37) (2 feet, 38, 4!, 511, 81, 1011, 1, 11,128, 133, 141)-13-[(>^-heteropropyl)methyl]-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-β-indole-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy
-3,5，8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
38) (21 ,38,41 ,51，81，101 ,1 11，128,138，141 )-13-[(二乙基氨基）甲基]-11 -[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8,10，12，14- 六甲基小氧—杂 _6—氮杂环十五烷 _15_酮； 38) (21,38,41,51,81,101,1 11,128,138,141 )-13-[(diethylamino)methyl]-11 -[[3,4,6-trideoxy-3 - (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 - small hexamethyl oxo - heteroaryl _ 6 - azetidin pentadecane _ 15 _-one;
39) (21¾，38，41，51 ,81，101 ,1 11 ,128，133,141 )-13-[(环戊基-氨基）甲基]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8,10，12，14- 六甲基 _1_氧-杂 _6·氮杂环十五垸 _15_酮； 39) (213⁄4, 38, 41, 51, 81, 101, 1 11 , 128, 133, 141)-13-[(cyclopentyl-amino)methyl]-11-[[3,4,6-trideoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14- hexamethyl _1_ oxo - 6 heteroaryl _ · azetidin fifteen embankment _1 _ 5-one;
40) (211，38，41，51，81，101，1 11 ,128，138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己 吡喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 -13-[(4-甲氧基 -苄基氨基） -甲 基] -3，5，8，10,12，14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  40) (211,38,41,51,81,101,1 11 ,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(4-methoxy-benzylamino)-methyl] -3,5,8 , 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
41) (2 38,41，51，81，101，1111,123,138,141 )-1 1-[[3,4,6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12，14-六甲基 -13-[(4-硝基 -苄基 氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮；  41) (2 38,41,51,81,101,1111,123,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-indole-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(4-nitro-benzyl) Amino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
42) (2R,3S,4R,5R,8R,10R,1 lR,12S，13S，14R)-13-[(4-氯 -苄基氨基）甲基] -1 1-[[3,4，6-三脱 氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 42) (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(4-chloro-benzylamino)methyl] -1 1-[[3,4, 6-Trideoxy-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy
-3，5,8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
43) (2 33,41 ,511,81 ,101 ,1 1 ,123,138,141 )-13-[(3，4-二氟-苄基氨基）甲基]-1 1-[[3，4，6-三 脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4，10，13-四羟基 -3,5，8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  43) (2 33,41 ,511,81 ,101 ,1 1 ,123,138,141 )-13-[(3,4-difluoro-benzylamino)methyl]-1 1-[[3,4,6- Trideoxy-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
44) (2R,3S,4R,5R,8R, 10R， 1 1 R， 12S， 13 S, 14R)- 11 - [[3，4，6-三脱氧 -3- (二甲基氨基；) -β-D-己 吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13- [(甲基- (吡啶 -4-基） -氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮； 替换页 （细则第 26条) 45) (211，38，41，511,81，101，111 ,128,138,14{1)-13-[(2,6-二氟-苄氨基）甲基]-1 1-[[3,4，6-三 脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 44) (2R,3S,4R,5R,8R, 10R, 1 1 R, 12S, 13 S, 14R)- 11 - [[3,4,6-Trideoxy-3-(dimethylamino;) - β-D-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- [ (Methyl-(pyridin-4-yl)-amino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one; replacement page (Article 26) 45) (211,38,41,511,81,101,111,128,138,14{1)-13-[(2,6-difluoro-benzylamino)methyl]-1 1-[[3,4 ,6-Trideoxy-3-(dimethylamino)-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
46) (21 ,38，41 ,51，811,1011，1 11，128，138，141 )-13-[(4-氟-苄基氨基）甲基]-11-[[3，4,6-三脱 氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 46) (21,38,41,51,811,1011,1 11,128,138,141 )-13-[(4-fluoro-benzylamino)methyl]-11-[[3,4,6 -triptylo-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy
-3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
47) (21，33，411,51 ,811,1011,1 11 ,123,138,141 )-13-[(3-氟-苄基氨基）甲基]-11-[[3，4,6-三脱 氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 -3,5,8,10，12，14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  47) (21,33,411,51,811,1011,1 11 ,123,138,141 )-13-[(3-Fluoro-benzylamino)methyl]-11-[[3,4,6-tripleoxy- 3-(Dimethylamino)-β-indole-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
48) (21，38，41 >51，811，1011,1111，128，138,1411)-13-[(2-氟-苄基氨基）甲基]-11-[[3，4,6-三脱 氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5,8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； 48) (21,38,41 > 51,811,1011,1111,128,138,1411)-13-[(2-fluoro-benzylamino)methyl]-11-[[3,4,6- Trideoxy-3-(dimethylamino)-PD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
49) (2^38，4! ,51，81，101 ,1 11，128，138，141 )-13-[(2，4-二氟-苄基氨基）甲基]-1 1-[[3,4，6-三 脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10,13-四羟基 -3，5，8,10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  49) (2^38,4!,51,81,101,1 11,128,138,141)-13-[(2,4-difluoro-benzylamino)methyl]-1 1-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-indole-hexyrylxyxy]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 , 5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
50) (2R,3S,4R,5R,8R,10R,l lR，12S,13S,14R)-13-[(2,5-二氟 -苄基氨基）甲基] -1 1-[[3，4,6-三 脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5,8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  50) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2,5-difluoro-benzylamino)methyl] -1 1-[[3 ,4,6-Trideoxy-3-(dimethylamino)-PD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
51) (21，38,411，51，811，101，1 11，125，138,141 )-13-[(3,5-二氟-苄基-氨基）甲基]-1 1-[[3，4,6- 三脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 51) (21,38,411,51,811,101,1 11,125,138,141 )-13-[(3,5-Difluoro-benzyl-amino)methyl]-1 1-[[3,4, 6-Trideoxy-3-(dimethylamino)-β-indole-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy
-3,5,8,10, 12,14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮； -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
52) (21，38，41 ,5]^811,1011，1 11 ,128，135,14 )-1 1 -[[3，4，6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -13-[4-(4-氟-苯基) -哌嗪小基-甲基] -3，4，10,13-四羟基 -3，5,8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  52) (21,38,41 ,5]^811,1011,1 11 ,128,135,14 )-1 1 -[[3,4,6-Trideoxy-3-(dimethylamino) -0 -hexylopyranosyl]oxy]-2-ethyl-13-[4-(4-fluoro-phenyl)-piperazine small-methyl]-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
53) (2R,3S,4R,5R,8R,10R,l lR,12S, 13S,14R)-13-[(2- 三 氟 甲 基 - 苄 基 氨 基 ） 甲 基 1-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四 羟基 -3，5,8,10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 53) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-trifluoromethyl-benzylamino)methyl1-11-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 , 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
54) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 13 - [(4- 三 氟 甲 基 - 苄 基 氨 基 ） 甲 基] -11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四 羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  54) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 13 - [(4-Trifluoromethyl-benzylamino)methyl]-11-[ [3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy- 3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
55) (2 ,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3- 三 氟 甲 基 - 苄 基 氨 基 ） 甲 基卜11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四 羟基 -3，5,8，10,12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  55) (2,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3-trifluoromethyl-benzylamino)methyl b 11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
56) (2R,3 S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R) -13-{[乙基 -(2-氟 -苯基） -氨基 ] -甲 基 }-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基卜 2-乙基 -3，4，10，13- 四羟基 -3，5，8，10，12, 14-六甲基- 氧-杂 -6-氮杂环十五烷 -15-酮；  56) (2R,3 S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R) -13-{[ethyl-(2-fluoro-phenyl)-amino]-methyl }-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexanopyranosyl]oxybu 2-ethyl-3,4,10,13 - tetrahydroxy-3,5,8,10,12,14-hexamethyl-oxy-hetero-6-azacyclopentadecane-15-one;
57) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[ 乙基 -(3-氟 -苯基） -氨基 ] - 甲  57) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[ethyl-(3-fluoro-phenyl)-amino]-
6  6
替换页 （细则第 26条) 基}-1 1-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,B- 四羟基 -3,5,8,10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) }}-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4, 10,B-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-6-nitrozacyclopentadecane-15-one;
58) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 13-[(2-氟 -6-三氟甲基-苄基-氨基）甲 基] -11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮  58) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 13-[(2-Fluoro-6-trifluoromethyl-benzyl-amino)methyl -11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10, 13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one
59) (21^，38,41，51 ,81 ,101 ,1 11，128,138,141 )-1 [[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13- [(甲基- (吡啶 -3-基) -氨基) -甲基 ]-1 -氧-杂 -6-氮杂环十五烷 -15-酮；  59) (21^,38,41,51,81,101,1 11,128,138,141 )-1 [[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexanpyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(methyl-(pyridine- 3-yl)-amino)-methyl]-1 -oxo-hetero-6-azacyclopentadecane-15-one;
60) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4-羟基 -3-甲氧基 -苄基氨基） -甲 基] -11 -[[3，4，6-三脱氧 -3-(二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四 羟基 -3,5，8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； 60) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4-hydroxy-3-methoxy-benzylamino)-methyl] -11 [[3, 4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
61) (2R,3 S,4R, 5R,8R, 1 OR, 1 1 R, 12S, 13 S , 14R)- 13 - {苯并 [1,3]二氧 -5-基 -氨基甲基） } -11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟 基 -3,5,8,10, 12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  61) (2R,3 S,4R, 5R,8R, 1 OR, 1 1 R, 12S, 13 S , 14R)- 13 - {Benzo[1,3]dioxo-5-yl-aminomethyl) } -11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10, 13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-6-azacyclopentadecane-15-one;
62) (21 ,38，41，51，81，101，1 11，128,138，1411)-1卜[[3,4,6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5，8，10,12,14-六甲基 -13-[(3-甲氧基-苄 基氨基) -甲基 ]-1 -氧-杂 -6-氮杂环十五烷 -15-酮； 62) (21,38,41,51,81,101,1 11,128,138,1411)-1Bu [[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(3-methoxy- Benzylamino)-methyl]-1 -oxo-hetero-6-azacyclopentadecane-15-one;
63) (21 ,38，411，511,81，101 ,1 11，128,133,141 )-13-[(2-甲氧基-苄基氨基)-甲基]-1 [[3，4，6- 三脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 -3，5,8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  63) (21,38,411,511,81,101,1 11,128,133,141 )-13-[(2-methoxy-benzylamino)-methyl]-1 [[3,4,6- III Deoxy-3-(dimethylamino)-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
64) (2R,3S,4R,5R,8R,10R,l l ,12S,13S,14R)-13-( (吡啶 -2-基） -氨基 -甲基 )-11-[[3，4，6- 三脱氧 -3- (二甲基氨基） -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  64) (2R, 3S, 4R, 5R, 8R, 10R, ll, 12S, 13S, 14R)-13-((pyridin-2-yl)-amino-methyl)-11-[[3,4,6 -Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
65) (2 ,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[ (2-甲氧基 -乙基氨基）甲基] -11-[[3，4,6- 三脱氧 -3- (二甲基氨基） -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 65) (2,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-methoxy-ethylamino)methyl]-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy
-3，5，8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
66) (2 ,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[(2-羟 基 -N- 甲 基 - 乙氨基 ] - 甲 基 }-11 -[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13- 四羟基 -3，5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  66) (2,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[(2-hydroxy-N-methyl-ethylamino)-methyl}-11-[ [3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy- 3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
67) (2¾38，41 ,511，81，101，1 11，128,138，141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5,8,10,12,14-六甲基 -13-{[(吡啶 -2-基- 甲基) -氨基] -甲基 }-1 -氧-杂 -6-氮杂环十五烷 -15-酮； 67) (23⁄438,41,511,81,101,1 11,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexidine Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{[(pyridine-2- Methyl-methyl)-amino]-methyl}-1 -oxo-hetero-6-azacyclopentadecane-15-one;
68) (2R,3 S，4R,5R,8R， 10R， 11 R, 12S， 13 S， 14R)- 13-[ (羟基氨基）甲基] - 11 -[[3 ,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5，8，10,12，14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  68) (2R,3 S,4R,5R,8R, 10R, 11 R, 12S, 13 S, 14R)- 13-[(hydroxyamino)methyl] - 11 -[[3,4,6-tripleoxy -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
69) (21，38，411,51，81，1011，1 11，128，138，141 )-13-{[(2-羟基-乙基)-氨基]-甲基}-11-[[3,4,6- 三脱氧 -3- (二甲基氨基） -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 替换页 （细则第 26条) -3,5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮； 69) (21,38,411,51,81,1011,1 11,128,138,141 )-13-{[(2-hydroxy-ethyl)-amino]-methyl}-11-[[3 ,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy replacement page Rule 26) -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
70) (21，38，41，51 ,81 ,101 ,1 1^128,138，141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基）- -0-己 吡喃木糖基]氧基] -2-乙基 -13-{[(3-氟-苯基)-甲基-氨基] -甲基 }-3,4，10，13-四羟基 -3,5,8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 70) (21,38,41,51,81,101,1 1^128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)- -0-hexyl Pyranopyranyl]oxy]-2-ethyl-13-{[(3-fluoro-phenyl)-methyl-amino]-methyl}-3,4,10,13-tetrahydroxy-3 , 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
71) (2R,3 S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14 )- 13 -[(6- 氯 - 吡 啶 -3- 基 - 氨 基 ） - 甲 基] -1 [[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四 羟基 -3，5，8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； 71) (2R,3 S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14 )- 13 -[(6-chloro-pyridin-3-yl-amino)-methyl] 1 [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra Hydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
72) (2R,3S,4R,5R,8R, 10R,1 1R,12S,13S,14R)-11-[[3 ,4,6-三脱氧 -3- (二甲基氨基）-β-ϋ-己 吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -13-[(4-羟基-正丁基氨基） -甲 基] -3,5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  72) (2R,3S,4R,5R,8R, 10R,1 1R,12S,13S,14R)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-ϋ -hexylopyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(4-hydroxy-n-butylamino)-methyl] -3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
73) 4-{(21，38，41 ,51，81 ,101 ,111，128,138,1411)-11-[[3,4，6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12，14-六甲基 -15-酮小氧-杂 -6-氮杂环 十五垸 -13-基-甲基] - 氨基 }-甲基-苯甲酸  73) 4-{(21,38,41,51,81,101,111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one small oxygen-hetero- 6-azetidine Hexadecyl-13-yl-methyl]-amino}-methyl-benzoic acid
74) (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13- (2-烯丙基-氨基） -甲基 -11-[[3，4,6-三脱 氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10，13-四羟基 -3，5，8,10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； 74) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13- (2-allyl-amino)-methyl-11-[[3,4,6-three Deoxy-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
75) (21，38，41，51 ,811，101，1 11 ,123，133,141 )-13-{[(3-氨基-1,4,4-三甲基-环己基-甲基）- 氨基] -甲基 }-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  75) (21,38,41,51,811,101,1 11 ,123,133,141 )-13-{[(3-amino-1,4,4-trimethyl-cyclohexyl-methyl)-amino ] -Methyl}-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3, 4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
76) (21，38，411，51 ,811，101 ,1 111，128,138，141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -13-{[2-(2-羟基-乙基-氨基) -乙基氨基] - 甲基 }-3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  76) (21,38,411,51,811,101,1 111,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexididine Iso-xylyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-{[2-(2-hydroxy-ethyl-amino)-ethylamino]-methyl} -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
77) (211，38，41 ,51 ,811,1011,1111，128,133,141 )-13-[(2-氯-4-甲氧-苄基氨基)-甲基]-1 [[3,4，6-三 脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5，8，10，12,14- 六甲基小氧-杂 .6_氮杂环十五院 _15·酮 77) (211, 38, 41, 51, 811, 1011, 1111, 128, 133, 141)-13-[(2-chloro-4-methoxy-benzylamino)-methyl]-1 [[3,4,6 -triptylo-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14- hexamethyloxy-hybrid. 6 _nitrogen heterocyclic fifteenth hospital _15·ketone
78) (2^，38，4!，511，811，101，1 11，128, 138，141 )-1 1 -[[3,4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12,14-六甲基 -13-[(1-甲基 -3-苯 基 *丙基-氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮；  78) (2^,38,4!,511,811,101,1 11,128, 138,141 )-1 1 -[[3,4,6-Trideoxy-3-(dimethylamino)-卩-0-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[ (1-methyl-3-phenyl*propyl-amino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
79) (2R,3S,4R，5R,8R，10R，l lR，12S，13S,14R)-l l-[[3,4，6-三脱氧 -3- (二甲基氨基） -β-D-己 吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-哌嗪-卜基-甲 基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 79) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-piperazine-基-Methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
80) (2R,3S,4R,5R,8R, 10R， 1 1 R， 12S， 13 S,14R)-11-[[3 ,4,6-三脱氧 -3- (二甲基氨基 )-p-D-己 吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-{ [(吡啶 -4-基- 甲基) -氨基] -甲基 1 _氧-杂 -6-氮杂环十五烷 -15-酮；  80) (2R,3S,4R,5R,8R, 10R, 1 1 R, 12S, 13 S,14R)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-pD -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{[(pyridine 4-yl-methyl)-amino]-methyl 1 _oxy-hetero-6-azacyclopentadecane-15-one;
81) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 13- { [(3-氯 -吡啶 -4-基） 甲基氨基 ] 甲 基}-11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基】氧基] -2-乙基 -3，4，10,13-四羟  81) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 13- { [(3-Chloro-pyridin-4-yl)methylamino]methyl} -11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13 -tetrahydroxyl
8 8
替换页 （细则第 26条) 基 -3，5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五院 -15-酮 Replacement page (Article 26) Base-3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentyl-15-ketone
82) N-{(2R,3 S,4R,5R,8R, 10R,1 1R,12S,13S,14R)-11-[[3 ,4,6-三脱氧 -3- (二甲基氨基 )-β-0- 己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12，14-六甲基 -15-酮 -1-氧-杂 -6-氮杂环十五烷 -13-基-甲基}-2，2,2-三氟-乙酰胺； 82) N-{(2R,3 S,4R,5R,8R, 10R,1 1R,12S,13S,14R)-11-[[3,4,6-Trideoxy-3-(dimethylamino) -β-0-hexylopyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15- Keto-1-oxo-hetero-6-azetidine pentadecyl-13-yl-methyl}-2,2,2-trifluoro-acetamide;
83) (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-{[(2-氯 -吡啶 -4-基-甲基） -氨基] -甲 基}-11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13- 四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 83) (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-{[(2-chloro-pyridin-4-yl-methyl)-amino]-methyl} -11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13 - tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
84) (21，38，41 ,51，81 ,101，111，123,138,141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃 木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13- (正戊基-氨基) -甲基 ]-3,5，8，10，12，14-六甲基小 氧-杂 -6-氮杂环十五烷 -15-酮  84) (21,38,41,51,81,101,111,123,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(n-pentyl-amino)-methyl]-3,5,8,10,12,14-six Methyl small oxygen-hetero-6-azacyclopentadecane-15-one
85) (2R,3S,4R,5R,8R,10R,1 1R,12S,13S,14R)-13-[(1H-苯并咪唑 -2-基 -氨基） -甲 基] -11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四 羟基 -3，5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  85) (2R,3S,4R,5R,8R,10R,1 1R,12S,13S,14R)-13-[(1H-benzimidazol-2-yl-amino)-methyl]-11-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 , 5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
86) (2R,3S,4R,5R,8R,10R,1 1 ,12S,13S,14R) -13-( ,Ν'-二甲基 -肼基 -甲基 )-11-[[3，4,6-三 脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 86) (2R,3S,4R,5R,8R,10R,1 1 ,12S,13S,14R) -13-( ,Ν'-dimethyl-indolyl-methyl)-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-indole-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy
-3,5,8,10, 12,14-六甲基 -1 -氧-杂 -6-氮杂环十五烷 -15-酮； -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
87) (2R,3S,4R,5R,8R, 1 OR, 11R, 12S, 13S, 14R)- 13-[(2,6-二氟 -4-甲氧 -苄基 -氨基）甲 基〗 -11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮  87) (2R, 3S, 4R, 5R, 8R, 1 OR, 11R, 12S, 13S, 14R)- 13-[(2,6-difluoro-4-methoxy-benzyl-amino)methyl] 11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13- Tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one
88) (21 ,38，41，51 ,81 ,101 ,1 111,128,133，1411)-1 1-[[3,4,6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-{[2-(2-羟基-乙氧基) -乙基氨基] -甲 基}-3，5，8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； 88) (21,38,41,51,81,101,1 111,128,133,1411)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexypyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-{[2-(2-hydroxy-ethoxy)-ethylamino]-methyl}-3, 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
89) (2¾,38，4! ,51，811,101 ,1 111,128，138，141 )-13-[(2-氯-乙基氨基)-甲基卜11-[[3,4，6-三脱 氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4，10,13-四羟基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  89) (23⁄4,38,4!,51,811,101,1 111,128,138,141)-13-[(2-chloro-ethylamino)-methylbu 11-[[3,4,6-tripleoxy -3-(Dimethylamino)-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 - hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
90) 2-{(21 ,38，41 ,51 ,811,101 ,111，128,138,1411)-11-[[3,4，6-三脱氧-3-(二甲基氨基）-3-0- 己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10，12,14-六甲基 -15-酮 -1-氧-杂 -6-氮杂环十五垸 -13-基-甲基] -氨基 }-丁酸；  90) 2-{(21 , 38,41 ,51 ,811,101 ,111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one-1-oxo- Hetero-6-azacyclopentadepin-13-yl-methyl]-amino}-butyric acid;
91) 3-{(21，38，41，51 ,81，101，1 111，128,138，141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基)-卩"0- 己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10，12,14-六甲基 -15-酮 -1-氧-杂 91) 3-{(21,38,41,51,81,101,1 111,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-indole "0-Pyrylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one- 1-oxo-hetero
-6-氮杂环十五烷 -13-基-甲基] -氨基 }-丙酸； -6-azacyclopentadecane-13-yl-methyl]-amino}-propionic acid;
92) (2 ,38，41，51 ,811,101，1 11 ,125,138，141¾ 11-[[3,4,6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -13-[(4-氟 -2-硝基-苯基氨基)-甲基] -3，4，10，13-四羟基 -3，5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  92) (2,38,41,51,811,101,1 11 ,125,138,1413⁄4 11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexylopyranosyl] Oxy]-2-ethyl-13-[(4-fluoro-2-nitro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
93) (211，38，41 ,511,81，101 ,1 11，128，133，141 )-13-[(4-溴-2-氟-苯基氨基)-甲基]-11-[[3,4,6- 三脱氧 -3-(二甲基氨基）-β-0-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3,5，8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 93) (211, 38, 41, 511, 81, 101, 11, 11, 128, 133, 141)-13-[(4-bromo-2-fluoro-phenylamino)-methyl]-11-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-0-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 , 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
9  9
替换页 （细则第 26条) 94) (21 ,38,41 ,51，81 ,101^111 ,125，138,141 )-13-[(4-溴-2-氨基-嘧啶)-甲基]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10，12，14-六甲 基 -1-氧-杂 -6-氮杂环十五烷 -15-酮 Replacement page (Article 26) 94) (21,38,41,51,81,101^111,125,138,141)-13-[(4-bromo-2-amino-pyrimidine)-methyl]-11-[[3,4,6 -triptylo-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
95) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,5-双-三氟甲基 -苯基氨基） -甲 基] -1 1 -[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四 羟基 -3，5，8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  95) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,5-bis-trifluoromethyl-phenylamino)-methyl] -1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13- Tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-6-azacyclopentadecane-15-one;
96) (2R,3 S，4R,5R,8R, 10R,1 1R, 12S, 13S， 14R)- 1 1 -[[3,4,6-三脱氧 -3- (二甲基氨基 )-β-ϋ-己 吡喃木糖基]氧基] -2-乙基 -13-[(2，4-二硝基 -苯基氨基) -甲基 ]-3，4，10,13-四羟基 -3，5,8，10,12，14-六甲基 -1 -氧-杂 -6-氮杂环十五垸 -15-酮；  96) (2R,3 S,4R,5R,8R, 10R,1 1R, 12S, 13S, 14R)- 1 1 -[[3,4,6-Trideoxy-3-(dimethylamino)-β -ϋ-hexylpyranosyl]oxy]-2-ethyl-13-[(2,4-dinitro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyl-1 -oxo-hetero-6-azacyclopentadecane-15-one;
97) (2R，3S,4R,5R，8R,10R，1 1R，12S，13S,14R)-1 [[3,4,6-三脱氧 -3- (二甲基氨基） -β-D-己 吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5，8，10，12，14-六甲基 -13-{ [(吗啉 -4-基- 甲基) -氨基] -甲基 } 1-氧-杂 -6-氮杂环十五垸 -15-酮； 97) (2R,3S,4R,5R,8R,10R,1 1R,12S,13S,14R)-1 [[3,4,6-Trideoxy-3-(dimethylamino)-β-D- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{[(morpholine) 4-yl-methyl)-amino]-methyl} 1-oxo-hetero-6-azacyclopentadecane-15-one;
98) (2R,3S,4R,5R,8R, 1 OR, 1 1R,12S, 13S, 14R)- 13-[(4-氨基 -吡 啶 -3-基 -氨基） - 甲 基] -1 1-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四 羟基 -3,5,8,10,12,14-六甲基 -1 -氧-杂 -6-氮杂环十五垸 -15-酮；  98) (2R,3S,4R,5R,8R, 1 OR, 1 1R,12S, 13S, 14R)- 13-[(4-Amino-pyridin-3-yl-amino)-methyl] -1 1- [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyl-1 -oxo-hetero-6-azacyclopentadecane-15-one;
99) (211,33,411，5] ，81{_,101 ,1 11 ,125，138,1411)-13-[(2-氯-苄基氨基）-甲基]-11-[[3,4，6-三脱 氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10,13-四羟基 -3，5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  99) (211,33,411,5],81{_,101,1 11 ,125,138,1411)-13-[(2-chloro-benzylamino)-methyl]-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-indole-hexyranose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
100) (21 ，38，41 ，51 ，811,101，1111,125，138，141 )-1 1-[[3,4，6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -13-[(2,4-二甲基 -苯基氨基) -甲基 ]-3,4,10,13-四羟基 100) (21,38,41,51,811,101,1111,125,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexanpyran Xylose]oxy]-2-ethyl-13-[(2,4-dimethyl-phenylamino)-methyl]-3,4,10,13-tetrahydroxy
-3，5,8,10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
101) (2 ，33,4!^,511，81 ，101 ,1 11 ,128,138,141 )-13-[(3-氯-苯基氨基)-甲基]-1卜[[3，4，6-三脱 氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 -3，5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  101) (2,33,4!^,511,81,101,1 11 ,128,138,141 )-13-[(3-chloro-phenylamino)-methyl]-1 b [[3,4,6- Trideoxy-3-(dimethylamino)-PD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
102)(2R，3S，4R,5R，8R，10R,1 lR,12S,13S，14R)-13-{[(5-氨基 -1 ,3,3-三甲基 -环己基甲基 1)- 氨基] -甲基 }-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基】-2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12,14-六甲基 -1 -氧-杂 -6-氮杂环十五垸 -15-酮； 102) (2R, 3S, 4R, 5R, 8R, 10R, 1 lR, 12S, 13S, 14R)-13-{[(5-amino-1,3,3-trimethyl-cyclohexylmethyl 1) -Amino]-Methyl}-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexanopyranosyl]oxy]-2-ethyl- 3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1 -oxo-hetero-6-azacyclopentadecane-15-one;
103) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-((2,3-二 氯 -6-硝基 -苄基氨基） 甲 基) -11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8, 10, 12， 14-六甲基- 1 -氧-杂 -6-氮杂环十五烷 -15-酮  103) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-((2,3-dichloro-6-nitro-benzylamino)methyl)-11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra Hydroxy-3,5,8,10,12,14-hexamethyl-1 1-oxo-hetero-6-azacyclopentadecane-15-one
104) (21 ,38,41 ，5 ，8]^，1011,1 11 ,128，138，141 )-13-[(4-氯-苯基氨基）-甲基]-11 -[[[3,4，6-三 脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5,8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  104) (21,38,41,5,8]^,1011,1 11 ,128,138,141 )-13-[(4-chloro-phenylamino)-methyl]-11 -[[[3 ,4,6-Trideoxy-3-(dimethylamino)-pD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
105) (211，38，41 ，51 ，81 ，101 ，1 11，128，138，141 )-11 -[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8,10,12,14-六甲基 -13- (喹啉 -6-基-氨 基甲基 )-1-氧-杂 -6-氮杂环十五垸 -15-酮；  105) (211,38,41,51,81,101,1 11,128,138,141 )-11 -[[3,4,6-Trideoxy-3-(dimethylamino)-卩-0 -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- (quinoline- 6-yl-aminomethyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
106) (211,38，41 ,511,81 ,1011，1 11 ，123,138，141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩"0-己  106) (211,38,41,511,81,1011,1 11 ,123,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime"0-hex
10 10
替换页 （细则第 26条) 吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -13-[(3-羟基 -丙基氨基） -甲 基] -3，5,8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-hydroxy-propylamino)-methyl]-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
107) (2R,3 S,4R,5R,8R, 1 OR, 1 1 R,l 2S, 13S， 14R)- 11-[[3,4,6-三脱氧 -3- (二甲基氨基）-p-D-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12，14-六甲基 -13- (吗啉斗基-氨 基甲基 )-1-氧-杂 -6-氮杂环十五垸 -15-酮；  107) (2R,3 S,4R,5R,8R, 1 OR, 1 1 R,l 2S, 13S, 14R)- 11-[[3,4,6-Trideoxy-3-(dimethylamino) -pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- ( Tropolide-aminomethyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
108) (2 ,3S,4R,5R,8R, 10R,1 1R,12S,13S,14R)- 1 1 -[[3,4,6-三脱氧 -3- (二甲基氨基）-β-ϋ-己 吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5，8，10，12,14-六甲基 -13-[(2-甲基氨基- 乙基氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五烷 -15-酮；  108) (2,3S,4R,5R,8R,10R,1 1R,12S,13S,14R)- 1 1 -[[3,4,6-Trideoxy-3-(dimethylamino)-β- ϋ-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(2 -methylamino-ethylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
109) (2R,3S,4R,5R,8 ,10R,1 1R,12S,13S,14R)-13-环庚基氨基甲基 -11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10，12，14- 六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  109) (2R,3S,4R,5R,8,10R,1 1R,12S,13S,14R)-13-cycloheptylaminomethyl-11-[[3,4,6-trideoxy-3- ( Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
110) 4-{(21，38，41 ,511，81，101，1 11，128，138，141 )-11-[[3，4，6，-三脱氧-3-(二甲基氨基)-卩-0- 己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5，8，10,12,14-六甲基 -1-氧 -15-酮-杂 -6-氮杂环十五烷 -13-基-甲基] -氨基 }-酞腈；  110) 4-{(21,38,41,511,81,101,1 11,128,138,141 )-11-[[3,4,6,-Trideoxy-3-(dimethylamino) -卩-0-hexylopyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1- Oxy-15-keto-hetero-6-azacyclopentadecane-13-yl-methyl]-amino}-phthalonitrile;
111)(21，33,41 ,5 ,811，1011,111 ,128,138,141 )-1 1-[[3，4,6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -13-{ [(呋喃 -2-基-甲基) -氨基] -甲基 }-3，4，10，13-四羟基 -3,5,8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； 111) (21, 33, 41, 5, 811, 1011, 111, 128, 138, 141)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Xylose]oxy]-2-ethyl-13-{[(furan-2-yl-methyl)-amino]-methyl}-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
112) (21，38，41 ,51，81 ,1011,1 11，123，133,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -13-[(3-甲氧基-苯氨基） -甲 基卜3,5,8,10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  112) (21,38,41,51,81,1011,1 11,123,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-methoxy-phenylamino)-methyl b 3,5,8,10 , 12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
113) (211,38,411,51，81，1011，1 11 ,128，138，1411)-13-[(3-溴-苯基氨基)-甲基]-1 1-[[3,4,6-三脱 氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  113) (211, 38, 411, 51, 81, 1011, 1 11 , 128, 138, 1411)-13-[(3-bromo-phenylamino)-methyl]-1 1-[[3,4,6 -triptylo-3-(dimethylamino)-β-indole-hexyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
1 14) (21 ,38,411,511,81 ,1011,1 111,128，133,141 )-11 -[[3，4,6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8,10,12,14-六甲基 -13-[(Ν-甲基-苯 基-氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五烷 -15-酮；  1 14) (21,38,411,511,81,1011,1 111,128,133,141 )-11 -[[3,4,6-Trideoxy-3-(dimethylamino)-indole-0-hexyranose ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(Ν-methyl-phenyl-amino) -methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
115) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-氨基 -1-甲基 -乙基氨基） -甲基] - 1 1-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟 基 -3，5,8,10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  115) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-amino-1-methyl-ethylamino)-methyl] - 1 1- [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
1 16)(211,33,41 ,511,81，1011，1 111,128,133，14] )-11-[[3，4,6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -13-[(4-乙炔基 -2H-吡唑 -3-基-氨基) -甲基 ]-3,4,10,13-四羟 基 *3,5，8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； 1 16) (211, 33, 41, 511, 81, 1011, 1 111, 128, 133, 14] )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyran Xylose]oxy]-2-ethyl-13-[(4-ethynyl-2H-pyrazol-3-yl-amino)-methyl]-3,4,10,13-tetrahydroxy*3 , 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
1 17) (2R,3S,4R,5R,8R, 1 OR, 1 1 R, 12S， 13S， 14R)-11 -[[3,4,6-三脱氧 -3- (二甲基氨基 )-β-ϋ-己 吡喃木糖基]氧基] -2-乙基 -13-[(4-乙基 -6-甲基 -[1，3，5]三氮唑 -2-基-氨基） -甲 基] -3，4，10，13-四羟基 -3,5,8,10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  1 17) (2R,3S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13S, 14R)-11 -[[3,4,6-Trideoxy-3-(dimethylamino)- ϋ-ϋ-Hexylpyranosyl]oxy]-2-ethyl-13-[(4-ethyl-6-methyl-[1,3,5]triazol-2-yl-amino -methyl] -3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
1 18) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4,6-二羟基 -嘧啶 -2-基-氨基） -甲 基] -1 1-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四  1 18) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4,6-dihydroxy-pyrimidin-2-yl-amino)-methyl] - 1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13 - four
11 11
替换页 （细则第 26条) 羟基 -3，5,8，10, 12,14-六甲基 -1 -氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) Hydroxy-3,5,8,10,12,14-hexamethyl-1 -oxo-hetero-6-azacyclopentadecane-15-one;
119)(2R，3S,4R，5R，8R,10R,11R，12S，13S，14R)-13-癸垸基氨基甲基 -1 1 -[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5，8，10，12，14- 六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； 119) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13-decylaminomethyl-1 1 -[[3,4,6-trideoxy-3- ( Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Methyl small oxygen-hetero-6-azacyclopentadecane-15-one;
120)3-{(21，38，41 ,51，81，101，1 11，128，138，141 )-1 1 -[[3,4，6-三脱氧-3-(二甲基氨基)-卩-0- 己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -15-酮 -1 -氧-杂 -6-氮杂环十五垸 -13-基-甲基] -氨基 } -正丁酸； 120) 3-{(21,38,41,51,81,101,1 11,128,138,141 )-1 1 -[[3,4,6-Trideoxy-3-(dimethylamino) -卩-0-hexylopyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15- Keto-1-oxo-hetero-6-azetidine, decaindole-13-yl-methyl]-amino}-n-butyric acid;
121) (21 ,38，411，511，811，1 (^,1 11 ,128,138,14] )-11-[[3，4，6-三脱氧-3-(二甲基氨基) "0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -13-[(1-羟基甲基 -丙基氨基） -甲 基] -3，5，8,10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  121) (21,38,411,511,811,1 (^,1 11 ,128,138,14] )-11-[[3,4,6-Trideoxy-3-(dimethylamino)"0- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(1-hydroxymethyl-propylamino)-methyl]-3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
122) (2R,3 S,4R,5R,8R,10R,1 1 R， 12S， 13 S， 14R)-1 1 -[[3,4,6-三脱氧 -3-(二甲基氨基 )-p-D-己 吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5，8，10，12，14-六甲基 -13-[(2-苯基 -丙基 氨基) -甲基 ]1-氧-杂 -6-氮杂环十五烷 -15-酮；  122) (2R,3 S,4R,5R,8R,10R,1 1 R, 12S, 13 S, 14R)-1 1 -[[3,4,6-Trideoxy-3-(dimethylamino) -pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[( 2-phenyl-propylamino)-methyl]1-oxo-hetero-6-azacyclopentadecane-15-one;
123)磺酸单 -2-{(2R,3S，4R,5R,8R,10R,l lR，12S,13S,14R)-l l-[[3,4,6-三脱氧 -3-(二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12,14-六甲基小氧 -15-酮 123) Sulfonic acid mono-2-{(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-trideoxy-3-(di) Methylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexa Small oxygen-15-ketone
-杂 -6-氮杂环十五垸 -13-基-甲基] -氨基 } -乙酯 -hetero-6-azacyclopentadecane-15-13-yl-methyl]-amino}-ethyl ester
124) (21 ,38,41，51，8] ,101 ,1 111，128，138，141 )-13-[(3，4-二氟-苯基氨基）-甲基]-1 1-[[3，4，6- 三脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  124) (21,38,41,51,8] ,101 ,1 111,128,138,141 )-13-[(3,4-difluoro-phenylamino)-methyl]-1 1-[ [3,4,6-Trideoxy-3-(dimethylamino)-β-indole-hexyrylxyxy]oxy]-2-ethyl-3,4,10,13-tetrahydroxy- 3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
125)(211，33，411,511，81 ,101 ,111 ,123,133,1411)-13-[(3,5-二氟-苄基氨基）-甲基]-11 -[[3,4,6- 三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12，14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮； 125) (211, 33, 411, 511, 81, 101, 111, 123, 133, 1411)-13-[(3,5-difluoro-benzylamino)-methyl]-11 -[[3,4,6- Triphos-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
126) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4,4-双甲氧基 -正丁基氨基） -甲 基] -1 1-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四 羟基 -3,5，8,10，12,14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  126) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4,4-bismethoxy-n-butylamino)-methyl] -1 1 -[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra Hydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
127) (211,38,411，51 ,811，1011,1 111，123,133，1411)-13-[(3，4-二氯-苄基氨基）-甲基]-1 [[3，4，6- 三脱氧 -3- (二甲基氨基） -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5，8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  127) (211, 38, 411, 51, 811, 1011, 1 111, 123, 133, 1411)-13-[(3,4-Dichloro-benzylamino)-methyl]-1 [[3,4,6- Triphos-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
128) (2 38，41，51，81，1011，1 11，128,138，141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -13-[(2-甲氧基 -乙基氨基） -甲 基卜 3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  128) (2 38,41,51,81,1011,1 11,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(2-methoxy-ethylamino)-methyl b 3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
129) (2R,3S，4R，5R，8R，10R,l lR,12S,13S,14R)-13-[(4-二乙基氨基- 1-甲基 -丁基氨基） -甲 基〗 - 1 1-[[3,4,6-三脱氧-3-(二甲基氨基) 0-己吡喃木糖基]氧基]-2-乙基-3，4，10，13- 四羟基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  129) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4-Diethylamino-1-methyl-butylamino)-methyl- 1 1-[[3,4,6-Trideoxy-3-(dimethylamino) 0-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
130) (2R,3S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 13 - [(3 -环 己基氨基 -丙基氨基） - 甲 基] -1 1-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四 羟基 -3，5,8,10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 130) (2R,3S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 13 - [(3-cyclohexylamino-propylamino)-methyl] -1 1- [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
12  12
替换页 （细则第 26条) 131) (21 ,38，41 ,511581，101，111，128，138，14 -13-((3,4-二氯苄基氨基）甲基)-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12,14-六甲 基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) 131) (21,38,41,511 5 81,101,111,128,138,14 -13-((3,4-dichlorobenzylamino)methyl)-11-[[3,4,6 -triptylo-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
132) (2R,3S,4R,5R,8R, 10R， 11 R，l 2S, 13S， 14R)- 11 -[[3,4,6-三脱氧 -3-(二甲基氨基）-β-ϋ-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12,14-六甲基 -13-[(1-甲基 -正丁 基氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮；  132) (2R,3S,4R,5R,8R, 10R, 11 R,l 2S, 13S, 14R)- 11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β- ϋ-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(1 -methyl-n-butylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
133) (21 ,38,41 ,51 ,81 ,1011，111 ,125，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -13-[(4-羟基 -3-甲氧基 -苄基氨基) -甲 基] 3,5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮：  133) (21,38,41,51,81,1011,111,125,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexididine Iso-xylyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(4-hydroxy-3-methoxy-benzylamino)-methyl] 3,5 , 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one:
134)(21，38,41 ,51 ,81 ,101 ,111，128，133,141 )-1 1-[[3,4,6-三脱氧-3-(二甲基氨基）-3-0-己 吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5,8，10，12，14-六甲基 -13-[(2-吡啶 -3-基- 乙基氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮； 134) (21, 38, 41, 51, 81, 101, 111, 128, 133, 141)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(2-pyridine- 3-yl-ethylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
135) (2! ,38,41，51，81，101，111 ,123，138，141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基）^-0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5，8，10,12，14-六甲基 -13-[(3-三氟甲基- 苄基氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五烷 -15-酮；  135) (2!,38,41,51,81,101,111,123,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)^-0 -hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(3- Trifluoromethyl-benzylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
136) (21，33，41 ,5] ,811，1011,111，125，138,141 )-13-[(2-氨基-苄基氨基)-甲基]-11-[[3,4，6-三 脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  136) (21,33,41,5] ,811,1011,111,125,138,141 )-13-[(2-Amino-benzylamino)-methyl]-11-[[3,4,6- Trideoxy-3-(dimethylamino)-PD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
137) (21，38，41，51 ,811,1011，111，123,138，141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基）- -0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8,10，12,14-六甲基 -13-{[(5-甲基-吡 唑 -2-基-甲基) -氨基] -甲基 }-1-氧-杂 -6-氮杂环十五垸 -15-酮；  137) (21,38,41,51,811,1011,111,123,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)- -0-hexanpyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{[(5-methyl- Pyrazol-2-yl-methyl)-amino]-methyl}-1-oxo-hetero-6-azacyclopentadecane-15-one;
138) (2 ,38,41，51，811，1011,111，123,133,141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基 ]-2-乙基 -3,4，10,13-四羟基 -13-[(3-甲氧基 -丙基氨基） -甲 基 3，5，8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  138) (2,38,41,51,811,1011,111,123,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-methoxy-propylamino)-methyl 3,5,8,10,12, 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
139)(211,38，41，511,811,1011,1111,128,138,141 )-13-[(环己基-甲基-氨基）-甲基]-11-[[3，4,6- 三脱氧 -3- (二甲基氨基） -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5，8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 139) (211, 38, 41, 511, 811, 1011, 1111, 128, 138, 141)-13-[(cyclohexyl-methyl-amino)-methyl]-11-[[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
140) (2 38,41 ,511,81，101，111 ,128，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）- -0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-[(1，2，2-三甲基 -丙基氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五烷 -15-酮；  140) (2 38,41 ,511,81,101,111 ,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)- -0-hexid Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(1,2,2 -trimethyl-propylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
141) (211，38,41，511,811,1011,111，128,138,1411)-11-[[3,4，6-三脱氧-3-(二甲基氨基）- -0-己 吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5,8，10，12，14-六甲基 -13- (哌啶 -4-基-氨 基甲基 )-1-氧-杂 -6-氮杂环十五垸 -15-酮；  141) (211, 38, 41, 511, 811, 1011, 111, 128, 138, 1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)--0-hexyryl xylose Ethyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(piperidin-4-yl-carbamate ))-1-oxo-hetero-6-azacyclopentadecane-15-one;
142) (2¾38，4!，51，81，101，111，128，138，141 )-1 [[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己 吡喃木糖基]氧基 ]-2-乙基 -13-[(2-氟 -苯基氨基） -甲基 ]-3,4,10,13-四羟基 142) (23⁄438,4!,51,81,101,111,128,138,141 )-1 [[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexidine Iso-xylyl]oxy]-2-ethyl-13-[(2-fluoro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy
-3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
143) (2R,3S,4R,5R,8R, 10R,11R,12S,13S,14R)-11-[[3 ,4,6-三脱氧 -3- (二甲基氨基） -β-D-己  143) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D- already
13  13
替换页 （细则第 26条) 吡喃木糖基]氧基 ]-2-乙基 -13-[(4-氟 -苯基氨基） -甲基 ]-3,4,10,13-四羟基 -3，5,8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； Replacement page (Article 26) Pyranopyranyl]oxy]-2-ethyl-13-[(4-fluoro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
144) (2 ,3 S,4R,5R,8R, 1 OR, 11 , 12S, 13 S, 14R)- 13-[(4-二 乙基氨基 -苯基氨基） - 甲 基] -1-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四 羟基 -3，5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  144) (2,3 S,4R,5R,8R, 1 OR, 11 , 12S, 13 S, 14R)- 13-[(4-diethylamino-phenylamino)-methyl] -1-[ [3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy- 3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
145) ^[(21，38,41 ,51，811，1011,11 ，123,138,141 )-11-[[[3,4,6-三脱氧-3-(二甲基氨基) -0- 己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -15-酮 -1-氧-杂 -6-氮杂环十五烷 -13-基-甲基] -苯甲酰胺；  145) ^[(21,38,41,51,811,1011,11,123,138,141 )-11-[[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexanpyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one-1-oxo-hetero- 6-azacyclopentadecane-13-yl-methyl]-benzamide;
146) (21，38，41 ,51，81，101 ,111，128，138,141 )-13-[(2,6-二氟-苯基氨基)-甲基]-11-[[3，4，6- 三脱氧 -3- (二甲基氨基） -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 146) (21, 38, 41, 51, 81, 101, 111, 128, 138, 141)-13-[(2,6-difluoro-phenylamino)-methyl]-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy
-3，5,8,10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
147) (21，38,41 ,51^，81，101，111，128,138,141 )-11-[[3,4>6-三脱氧-3-(二甲基氨基）-3-0-己 吡喃木糖基]氧基] -13-[N'-(2,4-二硝基-苯基) -肼基甲基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； 147) (21,38,41,51^,81,101,111,128,138,141 )-11-[[3,4 > 6-Trideoxy-3-(dimethylamino)-3-0-hexanpyran Xyllosyl]oxy]-13-[N'-(2,4-dinitro-phenyl)-indolylmethyl]-2-ethyl-3,4,10,13-tetrahydroxy-3 , 5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
148)(2R,3S,4R,5 ,8R,10R,l lR,12S,13S,14R)-13-[(6- 氯 - 吡 啶 -2- 基 - 氨 基 ） - 甲 基] -11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基卜 2-乙基 -3,4，10，13-四 羟基 -3,5,8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 148) (2R,3S,4R,5,8R,10R,l lR,12S,13S,14R)-13-[(6-chloro-pyridin-2-yl-amino)-methyl]-11-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyloxy-2-ethyl-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
149) (21，38,41，51，811，101，111，128,138，141 )-13-[(6-溴吡啶-2-基-氨基)-甲基]-1 [[3，4，6- 三脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  149) (21, 38, 41, 51, 811, 101, 111, 128, 138, 141)-13-[(6-bromopyridin-2-yl-amino)-methyl]-1 [[3,4,6 -Trideoxy-3-(dimethylamino)-PD-hexylopyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
150) (21，33,411,51，81 ,1011，111，123，133,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -13-肼基甲基 -3，4，10，13-四羟基 -3,5,8，10,12，14-六甲基 -1- 氧-杂 -6-氮杂环十五垸 -15-酮；  150) (21,33,411,51,81,1011,111,123,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-13-mercaptomethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo- Hetero-6-azacyclopentadecane-15-one;
151) (21，38，41 ,51 ,81，1011，111，128,133，141 )-13-[(3-氨基-苄基氨基)-甲基]-11-[[3,4,6-三 脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 151) (21, 38, 41, 51, 81, 1011, 111, 128, 133, 141)-13-[(3-amino-benzylamino)-methyl]-11-[[3,4,6-three Deoxy-3-(dimethylamino)-β-indole-hexyrylxyxy]oxy]-2-ethyl-3,4,10,13-tetrahydroxy
-3,5，8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
152) (2R,3S,4R,5R,8R,10R,l lR，12S,13S,14R)-13-[(2-氯 -苯基氨基) -甲基 ]-11-[[3,4,6-三脱 氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10，13-四羟基 -3，5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  152) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-chloro-phenylamino)-methyl]-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
153)(21 ,33,411,51 ,811，1011,1111,123,133,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基）-3-0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5，8,10,12，14-六甲基 -13-( '-苯基 -肼基 甲基) -1-氧-杂 -6-氮杂环十五垸 -15-酮； 153) (21, 33, 411, 51, 811, 1011, 1111, 123, 133, 141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexanpyranosyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-( '-phenyl-fluorenylmethyl) -1-oxo-hetero-6-azacyclopentadecane-15-one;
154) (2R,3S,4R,5R,8R, 1 OR, 1 1 R， 12S， 13 S， 14R)-11-[[3 ,4,6-三脱氧 -3- (二甲基氨基）-β-ϋ-己 吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 13-{[(1Η-吲哚 -3-基-甲基) -氨基] -甲 基}-3，5,8，10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  154) (2R,3S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R)-11-[[3,4,6-Trideoxy-3-(dimethylamino)- Ϋ-ϋ-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy 13-{[(1Η-吲哚-3-yl-methyl)-amino] -methyl}-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
155) (2 ,3S,4R,5R,8R,10R,l l ,12S,13S,14R)-13-[(4- 氯 -2-硝 基 - 苯 基 氨 基 ） - 甲 基】 -11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四  155) (2,3S,4R,5R,8R,10R,ll,12S,13S,14R)-13-[(4-chloro-2-nitro-phenylamino)-methyl] -11-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra
14 14
替换页 （细则第 26条) 羟基 -3，5,8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； Replacement page (Article 26) Hydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-6-azacyclopentadecane-15-one;
156)(211，38,41 ,51 ,81，101 ,1 11 ,128，138，1411)-13-[(3-氯-正丙基氨基)-甲基〗-11-[[3，4，6-三 脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10，13-四羟基 -3,5,8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； 156) (211, 38, 41, 51, 81, 101, 1 11 , 128, 138, 1411)-13-[(3-chloro-n-propylamino)-methyl-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
157)(2R,3S,4R,5R,8 ,10R,l lR,12S,13S,14R)-13-[(2-氯 -4- 硝 基 - 苯 基 氨 基 ） - 甲 基] -1 1-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四 羟基 -3，5,8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 157) (2R,3S,4R,5R,8,10R,l lR,12S,13S,14R)-13-[(2-chloro-4-nitro-phenylamino)-methyl]-1 1- [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
158) (211,38，41 ,51，81 ,101，111 ,128，135，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12，14-六甲基 -13-[(4-对-甲基苯 氧基 -苯基氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮；  158) (211,38,41,51,81,101,111,128,135,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(4-pair -methylphenoxy-phenylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
159) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,5-二氯 -吡啶 -4-基 -氨基） -甲 基] -11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四 羟基 -3，5,8,10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  159) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,5-Dichloro-pyridin-4-yl-amino)-methyl]-11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra Hydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
160) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3-氨 基 -吡啶 -2-基 -氨基） - 甲 基] -11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四 羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  160) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3-amino-pyridin-2-yl-amino)-methyl]-11-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 , 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
161) 1-{(211,38，411，51 ,81，101，111 ,123，138,141 )-[11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0- 己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂 环十五垸 -15-酮 -13-基-甲基] -氨基 } -咪唑 -2,4-二酮；  161) 1-{(211,38,411,51,81,101,111,123,138,141 )-[11-[[3,4,6-Trideoxy-3-(dimethylamino)-indole- 0-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6 -azacyclopentadecane-15-keto-13-yl-methyl]-amino}-imidazole-2,4-dione;
162)(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,5-二 甲 氧基 -苯 基氨基） - 甲 基〗 -11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基 2-乙基 -3,4,10,13-四 羟基 -3,5,8,10,12,14-六甲基 -15-酮 -1-氧-杂 -6-氮杂环十五垸； 162) (2R, 3S, 4R, 5R, 8R, 10R, l lR, 12S, 13S, 14R)-13-[(3,5-dimethoxy-phenylamino)-methyl] -11-[ [3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy 2-ethyl-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyl-15-one-1-oxo-hetero-6-azacyclopentadecane;
163) 3-{(211，38，41 ,5^811，101 ,111，128，138，1411)-[11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0- 己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5，8,10，12，14-六甲基 -15-酮 -1-氧-杂 -6-氮杂环十五垸 -13-基-甲基] -氨基) -噻吩 -2-羧酸甲酯；  163) 3-{(211,38,41,5^811,101,111,128,138,1411)-[11-[[3,4,6-Trideoxy-3-(dimethylamino)-卩-0-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one Methyl-1-oxo-hetero-6-azetidine-decadeta-13-yl-methyl]-amino)-thiophene-2-carboxylate;
164) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[3-氯 -1-(2-氯-乙基） -正丙基氨基] -甲 基 }-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13- 四羟基 -3,5，8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮  164) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[3-chloro-1-(2-chloro-ethyl)-n-propylamino] - Methyl}-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4, 10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-6-azacyclopentadecane-15-one
165) (2R,3S，4R，5R，8R,10R,l lR，12S，13S，14R)-l l-【[3，4，6-三脱氧 -3- (二甲基氨基） -β-D-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-[(3-羟基-吡啶 -2-基-氨基) -甲 基卜 3，5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  165) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-hydroxy-pyridin-2-yl-amino)-methyl b 3 , 5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
166) (21^33，41 ,51{_，811，1011，111，128,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-异丙基 -硫基 -甲基 -3，5，8，10，12，14-六 甲基- 氧-杂 -6-氮杂环十五垸 -15-酮；  166) (21^33,41,51{_,811,1011,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-isopropyl-thio-methyl-3,5,8,10,12,14 - hexamethyl-oxy-hetero-6-azacyclopentadecane-15-one;
167)(2 38,4!，51，81，101 ,1 1&，128，138,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基）-3-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-叔丁基 -硫基 -甲基 -3,5，8，10，12,14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； 167)(2 38,4!,51,81,101 ,1 1&,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-tert-butyl-thio-methyl-3,5,8,10,12,14- Hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
15  15
替换页 （细则第 26条) 168) (21，33,41 ,51，81，1011，1 11，128,138，1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13- (萘 -2-基 -硫基 -甲基)小氧-杂 -6-氮杂环十五烷 -15-酮； Replacement page (Article 26) 168) (21,33,41,51,81,1011,1 11,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- (naphthalen-2-yl-sulfur Methyl-methyl)oxy-hetero-6-azacyclopentadecane-15-one;
169) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-(4,5-二氢 -噻 唑 -2-基 -硫基 - 甲 基) -1 1-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四 羟基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  169) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-(4,5-dihydro-thiazol-2-yl-thio-methyl)-1 -[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra Hydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
170) (21 ,35，41 ,51 ,81 ,10 ,1 111,128,138，141 )-13-(2，3-二羟基-丙基-硫基-甲基)-11-[[3，4，6- 三脱氧 -3- (二甲基氨基） -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基- -3，5,8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  170) (21,35,41,51,81,10,1 111,128,138,141 )-13-(2,3-dihydroxy-propyl-thio-methyl)-11-[[3,4,6 -Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy--3,5,8 , 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
171)(21，38，41 ,51 ,81，101 ,1 1 ,128，138,1411)-1 1-[[3，4,6-三脱氧-3-(二甲基氨基） 0-己 吡喃木糖基]氧基] -2-乙基 -13- (呋喃 -2-基-甲基-硫基-甲基) -3，4,10，13-四羟基 -3，5,8,10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； 171) (21, 38, 41, 51, 81, 101, 1 1 , 128, 138, 1411)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino) 0-hexyl Pyranopyranyl]oxy]-2-ethyl-13-(furan-2-yl-methyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8 , 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
172) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-(2-二 乙基氨基 -乙基 -硫基 - 甲 基) -1 1 -[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四 羟基 -3，5,8，10,Π，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  172) (2R, 3S, 4R, 5R, 8R, 10R, l lR, 12S, 13S, 14R)-13-(2-diethylamino-ethyl-thio-methyl)-1 1 -[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 , 5,8,10,Π,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
173) (2R,3S,4R,5R,8R,10R,11R，12S，13S,14R)-13-苄基 -硫基 -甲基 -11-[[3，4,6-三脱氧 -3- (二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  173) (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-Benzyl-thio-methyl-11-[[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
174) (2R，3 S,4R,5R,8R,10R,1 1R,12S,13S,14R)- 1 1 -[[3，4,6-三脱氧 -3- (二甲基氨基）-β-ϋ-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8,10，12，14-六甲基 -13-Ρ-甲基苯-硫 基 -甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  174) (2R,3 S,4R,5R,8R,10R,1 1R,12S,13S,14R)- 1 1 -[[3,4,6-Trideoxy-3-(dimethylamino)-β -ϋ-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-fluorene- Methylbenzene-thio-methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
175) (21 ,35，41 ,51，811,101，1 111，123，138，141 )-13-(4-氯-苯基-硫基-甲基)-11-[[3，4，6-三脱 氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4，10，13-四羟基 -3，5,8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮：  175) (21,35,41,51,811,101,1 111,123,138,141 )-13-(4-chloro-phenyl-thio-methyl)-11-[[3,4,6- Trideoxy-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 ,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one:
176)(211,33,41，51，811，1011,1111,128,138,141 )-1 1-[[3,4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10，13-四羟基- -3，5，8，10,12，14-六甲基 -13-正丙基 -硫基 -甲基小氧-杂 _6_氮杂环十五垸 -15_酮； 176) (211, 33, 41, 51, 811, 1011, 1111, 128, 138, 141)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexanpyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 -5,8,10,12,14-hexamethyl-13-n-propyl-thio- Methyl small oxygen-hetero- 6 -nitrozacyclopentadepin-15-one;
177) 3-{(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)- 11-[[3，4,6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5，8，10，12，14-六甲基 -15-酮 -1-氧-杂 -6-氮杂环 十五垸 -13-基-甲基-硫基} -丙酸  177) 3-{(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)- 11-[[3,4,6-Trideoxy-3-(dimethylamino)-0 -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one-1- Oxy-hetero-6-nitrohecyclopentadepin-13-yl-methyl-thio}-propionic acid
178) (2R,3S,4R,5R,8R, 1 OR, 11 R, 12S,13S,14R)-11 -[[3 ,4,6-三脱氧 -3- (二甲基氨基）-β-ϋ-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8,10,12，14-六甲基 -13-苯基-硫基-甲 基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  178) (2R,3S,4R,5R,8R, 1 OR, 11 R, 12S,13S,14R)-11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β- ϋ-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-phenyl- Thio-methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
179) (2R，3S，4R，5R,8R，10R,1 1R,12S，I3S，14R)-13- (丁基-硫基-甲基） - 11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10, 13-四羟基 -3,5,8,10,12,14- 六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  179) (2R,3S,4R,5R,8R,10R,1 1R,12S,I3S,14R)-13-(butyl-thio-methyl)-11-[[3,4,6-tripleoxy -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
180) (211，38，41 ,511,81 ,10 ,1 11，125，133，1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基） -0-己  180) (211,38,41,511,81,10,11,125,133,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyl
16 16
替换页 （细则第 26条) 吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -13-(3-巯基-丙基-硫基-甲 基) -3,5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(3-indolyl-propyl-thio-methyl)-3,5,8,10 , 12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
181) (2R,3 S，4R，5R,8R, 1 OR, 11 R,l 2S, 13S, 14R)- 11 -[[3,4,6-三脱氧 -3- (二甲基氨基）_p-D-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12，14-六甲基 -13-戊基-硫基-甲 基 -1-氧-杂 -6-氣杂环十五垸 -15-酮；  181) (2R,3 S,4R,5R,8R, 1 OR, 11 R,l 2S, 13S, 14R)- 11 -[[3,4,6-Trideoxy-3-(dimethylamino)_p -D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-pentyl -thio-methyl-1-oxo-hetero-6-a gas heterocyclic pentacene-15-one;
182) (21 ,38,41，51，81 ,101 ,111 ,128,138,1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12,14-六甲基 -13-己基-硫基-甲 基 -1-氧-杂 -6-氮杂环十五烧 -15-酮；  182) (21,38,41,51,81,101,111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexidyl Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-hexyl-thio-methyl -1-oxo-hetero-6-azacyclopentadecane-15-one;
183) (21 ,38，41 ,51 ,81，101 ,1111,128,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-3-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -13-辛基-硫基-甲 基小氧-杂 -6-氮杂环十五烷 -15-酮；  183) (21,38,41,51,81,101,1111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexidyl Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-octyl-thio-methyl Small oxygen-hetero-6-azacyclopentadecane-15-one;
184) (21，38，41,51，81，101 ,111^128,138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8，10，12，14-六甲基 -13-十二垸基-硫 基 -甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  184) (21,38,41,51,81,101,111^128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranidyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-dodedecyl-thio-methyl- 1-oxo-hetero-6-azacyclopentadecane-15-one;
185)(21 ,33，41，511，811,101，111，123,133,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基 ]-2-乙基 -13-(3-氟 -苄基 -硫基 -甲基）-3,4,10,13-四羟基 -3,5,8,10,12,14*六甲基小氧-杂 -6-氮杂环十五烷 -15-酮； 185) (21, 33, 41, 511, 811, 101, 111, 123, 133, 1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranopyranosyl ]oxy]-2-ethyl-13-(3-fluoro-benzyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8,10,12,14* Hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
186) (21 ,38，41，51，81，1011,111，128，138，141 )-13-(苯并噻唑-2-基-硫基-甲基)-11-[[3，4,6- 三脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5，8,10,12,14*六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  186) (21, 38, 41, 51, 81, 1011, 111, 128, 138, 141)-13-(benzothiazol-2-yl-thio-methyl)-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12, 14* hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
187) {(21,38,411,5 81 ,101，111 ,128,138，141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-3-0-木- 吡喃糖基） ]-2.氧 -2-乙基 -3，4,10，13-四羟基 -3，5，8,10，12，14-六甲基 -15-酮小氧-杂 -6- 氮杂环十五烷 -13-基-甲基-硫基] } -乙酸  187) {(21,38,411,5 81 ,101,111 ,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-wood-pyran Glycosyl)]-2. Oxy-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one small oxygen-hetero-6 - Azacyclopentadecane-13-yl-methyl-thio] } -acetic acid
188) (211,38,41，51，81 ,101 ,1111，123,133，141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基 ]-2-乙基 -13-(4-氟 -苯基 -硫基 -甲基）-3,4,10,13-四羟基 188) (211, 38, 41, 51, 81, 101, 1111, 123, 133, 141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexidine Iso-xylyloxy]-2-ethyl-13-(4-fluoro-phenyl-thio-methyl)-3,4,10,13-tetrahydroxy
-3，5,8,10，12,14六甲基小氧-杂 -6-氮杂环十五烷 -15-酮； -3,5,8,10,12,14 hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
189) (211，38，411，511，81，101，111，128，138,141)-1 [[3，4,6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -13-异丁基 -硫基 -甲基 -3,5,8，10,12，14-六 甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  189) (211,38,411,511,81,101,111,128,138,141)-1 [[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyryl xylose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-isobutyl-thio-methyl-3,5,8,10,12,14-hexamethyl Oxy-hetero-6-azacyclopentadecane-15-one;
190)(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R) - 11 -[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃 木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-{ (仲-丁基-硫基） -甲基 }-3,5，8,10，12，14-六甲 基 -1-氧-杂 -6-氮杂环十五烷 -15-酮 190) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R) - 11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β-D- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-{(sec-butyl-thio)-methyl}-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
191) (211,38,41 ,511,81 ,101，111 ,128，138,141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基）-3-0-己 吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -13-(2-硫醇-乙基-硫基-甲 基) -3，5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  191) (211,38,41,511,81,101,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexididine Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(2-thiol-ethyl-thio-methyl)-3,5,8,10 , 12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
192) (211,35,41 ,511,81^101,1111,128,138,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基）-&-0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8,10，12，14-六甲基 -13-(3-甲基-丁基-  192) (211, 35, 41, 511, 81^101, 1111, 128, 138, 1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-&-0-hexid Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(3-methyl-butyl Base -
17 17
替换页 （细则第 26条) 硫基-甲基) -1-氧-杂 -6-氮杂环十五烷 -15-酮； Replacement page (Article 26) Thio-methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
193)(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-(1H-苯 并 咪 唑 -2-基 -硫 基 - 甲 基) -1 1-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10，13-四 羟基 -3，5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 193) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13-(1H-benzimidazol-2-yl-thio-methyl)-1 1[[3 ,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
194)(21 ,38,41，51 ,81 ,101，111 ,128，138，141 )-1 1-[[3,4,6-三脱氧-3-(二甲基氨基) -0-己 吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -13-(4-羟基-苯基-硫基-甲 基) -3,5,8,10,12 14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； 194) (21, 38, 41, 51, 81, 101, 111, 128, 138, 141)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(4-hydroxy-phenyl-thio-methyl)-3,5,8,10 , 12 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
195) (21，38,41 ,51，811,10]，1 11，128，138，141 )-13-[(烯丙基-硫基)-甲基]-1 1-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  195) (21, 38, 41, 51, 811, 10], 11, 11, 128, 138, 141)-13-[(allyl-thio)-methyl]-1 1-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
196) (2R,3S,4R,5R,8R, 10R， 11R，12S, 13S, 14R)- 1 1 -[[3 ,4,6-三脱氧 -3- (二甲基氨基 )-β-ϋ-己 吡喃木糖基]氧基 ]-2-乙基 -3，4，10,13-四羟基 -13-(5-硫醇-戊基-硫基-甲 基) -3，5，8，10，12>14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  196) (2R,3S,4R,5R,8R, 10R, 11R,12S, 13S, 14R)- 1 1 -[[3,4,6-Trideoxy-3-(dimethylamino)-β-ϋ -hexylopyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(5-thiol-pentyl-thio-methyl)-3,5, 8,10,12>14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
197) 1^-{4-[(21，38,41，51 ,811,101 ,1111,128，133,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8，10,12，14-六甲基 -15-酮 -1-氧-杂 -6-氮杂 环十五垸 -13-基 ^甲基-硫基] -苯基 }-乙酰胺  197) 1^-{4-[(21,38,41,51,811,101,1111,128,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-indole -0-hexylopyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one- 1-oxo-hetero-6-azacyclopentadecane-13-yl^methyl-thio]-phenyl}-acetamide
198) (21 ,38，411，51，81，101，1 111，128,138，141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基〗氧基 ]-2-乙基 -3，4，10,13-四羟基 -13-C6-硫醇-己基-硫基-甲 基) -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  198) (21,38,411,51,81,101,1 111,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0- Hexylpyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-C6-thiol-hexyl-thio-methyl) -3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
199)(211，38,41^，51，81，101 ,1 111,128，138，141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -13-(8-硫醇 -正庚基-硫基-甲 基) -3,5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮； 199) (211, 38, 41^, 51, 81, 101, 1 111, 128, 138, 141)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0 -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(8-thiol-n-heptyl-thio-methyl)-3,5 , 8, 10, 12, 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
200) (2 ，38，41，51 ,811,1011，1111，123,133,14 -11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧;基 ]-2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12,14-六甲基 -13- (吡啶 -2-基-硫 基.甲基) -1-氧-杂 -6-氮杂环十五烷 -15-酮；  200) (2,38,41,51,811,1011,1111,123,133,14 -11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexanpyran Xylose]oxy]yl]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(pyridin-2-yl- Thiomethyl.methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
201) (2R,3S,4R,5R，8R，10R，11R,12S，13S，14R)-1 [[3,4，6-三脱氧 -3- (二甲基氨基） -β-D-己 吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10，12，14-六甲基 -13- (壬基-硫基) - 甲基 -1-氧-杂 -6氮杂环十五垸 -15-酮；  201) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-1 [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(mercapto-thio ) - methyl-1-oxo-hetero-6azacyclopentadecane-15-one;
202) (2R,3S,4R,5R,8R.,10R,11R,12S,13S,14R)-11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃 木糖基]氧基 ]-2+乙基 -3,4,10,13-四羟基 -13-((6-羟基-己基-硫基)甲基) -3,5,8,10,12,14-六甲 基 -1-氧-杂 -6-氮杂环十五垸 -15-酮  202) (2R,3S,4R,5R,8R.,10R,11R,12S,13S,14R)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D -Hexylpyranosyl]oxy]-2+ethyl-3,4,10,13-tetrahydroxy-13-((6-hydroxy-hexyl-thio)methyl)-3,5,8 ,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
203) (2R,3S，4R,5R，8R，10R，l lR,12S,13S，14R)-l l-[[3，4，6-三脱氧 -3- (二甲基氨基） -β-D-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12，14-六甲基 -13-正庚基-硫基- 甲基 1-氧-杂 -6，氮杂环十五烷 -15-酮；  203) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-n-heptyl -thio-methyl 1-oxo-hetero-6, azacyclopentadecane-15-one;
204)(2R,3S,4R，5R,8R，10R,l lR,12S,13S,14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基） -β-D-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12，14-六甲基 -13-(2-甲基-丁基- 硫基-甲基) -1-氧-杂 -6-氮杂环十五烷 -15-酮； 204) (2R, 3S, 4R, 5R, 8R, 10R, l lR, 12S, 13S, 14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(2- Methyl-butyl-thio-methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
18  18
替换页 （细则第 26条) 205) (211，38，411，51，81，101，111，128，138，1411)-13-(2，4-二氟-苯基-硫基-甲基)-1 [[3,4,6-三 脱氧 -3-(二甲基氨基 )-β-ϋ-己吡喃木糖基】氧基 ]-2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) 205) (211, 38, 411, 51, 81, 101, 111, 128, 138, 1411)-13-(2,4-difluoro-phenyl-thio-methyl)-1 [[3,4 ,6-Trideoxy-3-(dimethylamino)-β-indole-hexyranose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
206) (211，33，41 ,51 ,81 ,1011,111 ,128,138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5，8，10，12,14-六甲基 -13- (吡啶 -2-基-甲 基-硫基-甲基)小氧-杂 -6-氮杂环十五垸 -15-酮；  206) (211, 33, 41, 51, 81, 1011, 111, 128, 138, 141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(pyridin-2-yl-methyl -thio-methyl)oxy-hetero-6-azacyclopentadecane-15-one;
207) (21 ,33,41，51 ,811,1011,1111，128,138,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基) -0-己 吡喃木糖基]氧基] -13-(1，2-二甲基 -丙基 -硫基 -甲基 )-2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  207) (21,33,41,51,811,1011,1111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranium Glycosyl]oxy]-13-(1,2-dimethyl-propyl-thio-methyl)-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
208)(21 ,38,4 ,511，81 ,101^111 ,128,138,141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基）- -0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10，12,14-六甲基 -13-(1-甲基-丁基- 硫基-甲基) -1-氧-杂 -6-氮杂环十五垸 -15-酮； 208)(21,38,4,511,81,101^111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)--0-hexyryl xylose Ethyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(1-methyl-butyl-sulfur -methyl)-1-oxo-hetero-6-azetidine, deca-decyl-15-one;
209) (2R,3 S,4R，5R，8R, 1 OR, 11 R，l 2S, 13S， 14R)- l l-[[3 ,4,6-三脱氧 -3- (二甲基氨基）-β-0-己 吡喃木糖基]氧基] -2-乙基 -13- (乙基-硫基) 甲基 -3,4,10,13-四羟基 -3,5,8,10,12,14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  209) (2R,3 S,4R,5R,8R, 1 OR, 11 R,l 2S, 13S, 14R)- l l-[[3,4,6-Trideoxy-3-(dimethylamino) -β-0-hexylpyranosyl]oxy]-2-ethyl-13-(ethyl-thio)methyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
210) (21 ,38,41，51，811,101，111，128,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -13- (甲基-硫基) 甲基 -3,4,10,13-四羟基 -3,5,8，10，12，14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  210) (21,38,41,51,811,101,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-13-(methyl-thio)methyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl -1-oxo-hetero-6-azacyclopentadecane-15-one;
211) (211,38,41，51 ,81 ,1011，1111，123,138，141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基） -0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12,14-六甲基 -13- (邻-甲苯-硫基) 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  211) (211,38,41,51,81,1011,1111,123,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranium Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(o-tolyl-thio) A Keith-1-oxo-hetero-6-azacyclopentadecane-15-one;
212) (211,38，41，51，811,1011，111，128，138，141 )-1 [[3，4，6-三脱氧-3-(二甲基氨基）-3-0-己 吡喃木糖基〗氧基 ]-2-乙基 -3,4，10，13-四羟基 -13-(4-硫醇-戊基-硫基-甲 基) -3,5，8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮  212) (211,38,41,51,811,1011,111,128,138,141 )-1 [[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyl Pyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(4-thiol-pentyl-thio-methyl)-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
213)(2 ，33,41 ,51 ,811,1011,1111,123,138，1411)-11-[[3,4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基] -2-乙基 -13-(3，4-二氟-苯基-硫基-甲基) -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； 213) (2,33,41,51,811,1011,1111,123,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexidyl Iso-xylyl]oxy]-2-ethyl-13-(3,4-difluoro-phenyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8 , 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
214) (21，38,41，51，81，101，1111,128,133，141 -11-[[3,4,6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基 ]-2-乙基 -13-(3-氟 -苯基 -硫基 -甲基）-3,4,10,13-四羟基 -3,5,8,10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  214) (21,38,41,51,81,101,1111,128,133,141 -11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexanpyran Xylose]oxy]-2-ethyl-13-(3-fluoro-phenyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
215) (2!^,38，41 ,511，81，101 ,111 ,128,138，141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基 ]-2-乙基 -13-(4-氟 -苄基 -硫基 -甲基）-3，4,10，13-四羟基 -3,5，8,10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  215) (2!^,38,41,511,81,101,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0- Hexylpyranosyl]oxy]-2-ethyl-13-(4-fluoro-benzyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
216) (211,33，41，51，81，101，111，123,133，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己 吡喃木糖基]氧基 ]-2-乙基 -13-(2-氟 -苄基 -硫基 -甲基）-3，4，10,13-四羟基 216) (211,33,41,51,81,101,111,123,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexidyl Iso-xylyloxy]-2-ethyl-13-(2-fluoro-benzyl-thio-methyl)-3,4,10,13-tetrahydroxy
-3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
217) (2R,3S,4R,5R,8R,10R,1 lR,12S，13S,14R)-13-(4-氯-苄基-硫基-甲基) -11-[[3，4，6-三脱  217) (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-(4-chloro-benzyl-thio-methyl)-11-[[3,4, 6-triple
19 19
替换页 （细则第 26条) 氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； 本发明还提供一种本发明上述化合物的药学上可接受的盐， 其中， 所述化合物的药学上 可接受的盐为所述化合物与酸反应生成的， 其中所述酸为无机酸或有机酸。 Replacement page (Article 26) Oxy-3-(dimethylamino)-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, A pharmaceutically acceptable salt of the above compound of the present invention, wherein the pharmaceutically acceptable salt of the compound is further provided as a pharmaceutically acceptable salt of the compound of the present invention An acceptable salt is formed by reacting the compound with an acid, wherein the acid is an inorganic or organic acid.
本发明还提供上述化合物或其药学上可接受的盐在制备治疗哺乳动物、 鱼或鸟的细菌感 染或原生动物感染的药物中的用途； 或本发明所述化合物在合成其他大环内酯抗菌素中间 体的用途。  The present invention also provides the use of the above compound or a pharmaceutically acceptable salt thereof for the preparation of a medicament for treating a bacterial infection or a protozoal infection of a mammal, fish or bird; or the compound of the present invention for synthesizing other macrolide antibiotics The use of intermediates.
本发明还提供一种组合物， 其包含本发明所述的化合物或其药学上可接受的盐， 以及药 学上可以接受的载体。  The invention also provides a composition comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
下面合成路线描述了本发明的通式（ I )化合物，涉及所有的原料都是通过这些示意图 中描述的方法、 通过有机化学领域普通技术人员熟知的方法制备的或者商购。 本发明的 全部标题化合物都是通过这些示意图中描述的方法制备的， 这些方法是有机化学领域普 通技术人员熟知的。  The following synthetic schemes describe the compounds of formula (I) of the present invention, and all of the starting materials are prepared by the methods described in these schematics, by methods well known to those of ordinary skill in the art of organic chemistry, or commercially. All of the title compounds of the present invention are prepared by the methods described in these schematics, which are well known to those skilled in the art of organic chemistry.
Figure imgf000021_0001
Figure imgf000021_0001
20  20
替换页 （细则第 26条)
Figure imgf000022_0001
Replacement page (Article 26)
Figure imgf000022_0001
通式 V 通式 (l >  General formula V general formula (l >
起始化合物 1可按照本领域技术人员熟知的合成方法，包括 US4474768和 US4517359 中描述的合成方法制备或者商购。  The starting compound 1 can be prepared or commercially available according to synthetic methods well known to those skilled in the art, including the synthetic methods described in U.S. Patent 4,474,768 and U.S. Patent 4,517,359.
步骤 a中， 化合物 1中 C-2'羟基通过用等当量的乙酸酐在二氯甲垸中在无外部碱存 在的条件下处理化合物 1可选择性地被保护， 得到其中 R4是乙酰基的通式 II化合物。 可 用甲醇在 23~65'C处理通式 II化合物 10~48小时除去乙酰基保护基。 C-2'的羟基还可使用 本领域技术人员熟知的其它羟基保护基， 如苄氧羰基 (Cbz)保护， 期间 C-4"的羟基也会被 保护，但不影响后续实验。 C-2'羟基可通过用氯甲酸苄酯在四氢呋喃和水中处理通式 II化 合物在一步中使用 Cbz选择性被保护。 Cbz基团可使用常规的催化氢化除去， 也可以使 用本领域中熟知的在适当的有机溶剂中在约室温至约 100'C的温度范围内反应 2h〜5天 即可除掉。 在下面的描述中， C-2'和 C-4"的羟基是以本领域的技术人员认为的适当形式 被保护或脱保护的。  In the step a, the C-2' hydroxyl group in the compound 1 can be selectively protected by treating the compound 1 with an equivalent amount of acetic anhydride in methylene chloride in the absence of an external base, wherein R4 is an acetyl group. a compound of formula II. The acetyl protecting group can be removed by treating the compound of formula II with methanol at 23~65'C for 10 to 48 hours. The hydroxyl group of C-2' can also be protected using other hydroxy protecting groups well known to those skilled in the art, such as benzyloxycarbonyl (Cbz), during which the hydroxyl group of C-4" is also protected, but does not affect subsequent experiments. 'Hydroxyl can be protected by treatment with a benzyl chloroformate in tetrahydrofuran and water in a compound of formula II using Cbz selectivity in one step. The Cbz group can be removed using conventional catalytic hydrogenation, or it can be used in a suitable manner as is well known in the art. The organic solvent can be removed by reacting for 2 to 5 days in a temperature range of about room temperature to about 100 ° C. In the following description, the hydroxyl groups of C-2' and C-4" are considered by those skilled in the art. The proper form is protected or deprotected.
步骤 b中， SP : 对于 C-3位克拉定糖的脱除， 使用本领域技术人员熟知的脱除方法， 在乙醇 /水中使用盐酸进行脱除即得脱糖化合物通式 III。  In step b, SP: For the removal of the C-3 claratin sugar, the de-sugaring compound of the formula III is obtained by removing it with hydrochloric acid in ethanol/water using a removal method well known to those skilled in the art.
步骤 c中， 对通 i式 III的 C-3的羟基进行氧化。 对母核的合成焦点集中 C-3位羟基的 氧化问题上。 通过本领域技术人员熟知的方法， 包括一种或多种描述于 Jcrnmal of Anti-biotics,1988, 1029-1047页中的方法，将通式 III中的 C-3羟基氧化为相应的酮。例如， 通式 IV的酮可用二甲亚砜和合适的活化剂制备。 常规用于氧化的反应条件包括： 如： a) Corey-kim氧化： J. Med. Chem ,2001, 44 (24)： 4137〜4156 ； b) Jone's试剂： Bioorg. Med. Chem. Lett,2006, 16 (3)： 569〜572. ； c) Dess-martin's试剂: US 2004/0254126 ； d) 改 进的 Pfitzner-maffat氧化： J. Med. Chem , 1998, 41 ( 21)： 4080〜4100;e) Moffatt氧化， 使 用 N-乙基 -N'-(N, N-二甲基氨基丙基)碳二亚胺和二甲亚砜在三氟乙酸吡啶鏠盐存在下反 应； 或 f) Swem氧化， 其中草酸氯和二甲亚砜在二氯甲烷中反应， 接着加入三乙胺或三 氟乙酸酐和二甲亚砜在二氯甲垸中反应， 接着加入三乙胺等。  In the step c, the hydroxyl group of C-3 of the formula III is oxidized. The synthesis focus on the mother nucleus concentrates on the oxidation of the hydroxyl group at the C-3 position. The C-3 hydroxyl group of formula III is oxidized to the corresponding ketone by methods well known to those skilled in the art, including one or more of the methods described in Jcrnmal of Anti-biotics, 1988, pages 1029-1047. For example, a ketone of formula IV can be prepared using dimethyl sulfoxide and a suitable activator. The reaction conditions conventionally used for oxidation include: a) Corey-kim oxidation: J. Med. Chem, 2001, 44 (24): 4137~4156; b) Jone's reagent: Bioorg. Med. Chem. Lett, 2006, 16 (3): 569~572.; c) Dess-martin's reagent: US 2004/0254126; d) Improved Pfitzner-maffat oxidation: J. Med. Chem, 1998, 41 ( 21): 4080~4100; e) Moffatt oxidation, using N-ethyl-N'-(N,N-dimethylaminopropyl)carbodiimide and dimethyl sulfoxide in the presence of pyridinium trifluoroacetate; or f) Swem oxidation, Among them, oxalic acid chloride and dimethyl sulfoxide are reacted in dichloromethane, followed by the addition of triethylamine or trifluoroacetic anhydride and dimethyl sulfoxide in dichloromethane, followed by the addition of triethylamine and the like.
在步骤 c中氧化方法优选：二甲亚砜和三氟乙酸酐和三乙胺来氧化。 -78°C〜50'C下， 优选 -78Ό〜- 60'C，保护后的脱糖物溶解到适当的溶剂中，所用溶剂为：二氯甲垸，丙酮， 乙酸乙酯， 乙酸异丙酯等， 优选二氯甲烷， 而后加入三氟乙酸酐， 优选滴加， 反应 0〜 3h， 取三乙胺滴加， 反应 0〜3h， 反应完毕处理即得氧化物通式 IV。  The oxidation method in step c is preferably dimethyl sulfoxide and trifluoroacetic anhydride and triethylamine for oxidation. -78 ° C ~ 50 ° C, preferably -78 Ό ~ - 60 'C, the protected defatted material is dissolved in a suitable solvent: dichloromethyl hydrazine, acetone, ethyl acetate, isopropyl acetate The ester or the like is preferably dichloromethane, and then trifluoroacetic anhydride is added, preferably dropwise, and the reaction is carried out for 0 to 3 hours. Triethylamine is added dropwise, and the reaction is carried out for 0 to 3 hours.
在步骤 c中更优选： 使用 1-乙基 -(3-二甲基氨基丙基)碳酰二亚胺盐酸盐 /二甲亚砜在 二氯甲烷中与通式 III化合物， 搅拌， 冷却至 -15°C〜25 °C , 优选 0°C , 加入三氟乙酸吡啶盐氯  More preferably in step c: using 1-ethyl-(3-dimethylaminopropyl)carbonyldiimide hydrochloride/dimethylsulfoxide in dichloromethane with a compound of formula III, stirring, cooling To -15 ° C ~ 25 ° C, preferably 0 ° C, adding trifluoroacetic acid pyridinium chloride
21  twenty one
替换页 （细则第 26条) 代烃溶液， 控制温度 3'C以下， 反应完毕处理即得氧化物通式 IV。 Replacement page (Article 26) The hydrocarbon generation solution has a controlled temperature of 3'C or less, and the reaction is completed to obtain the oxide of the general formula IV.
在步骤 d中， ¾式 化合物可用两种方法获得。  In step d, the compound of the formula 3b can be obtained in two ways.
在第一种方法 (方法 A)中， 用 (CH3)3S(0)X2， 其中 X2是卤素， -BF4, 或 -PF6，其中卤 素优选是碘， 在碱如叔丁醇钾， 叔丁醇钠， 乙醇钠， 氢化钠， 1,1,3,3-四甲基胍， 1,8-二氮 杂双环 [5. 4. 0]十一 -7-烯， 1,5-二氮杂双环 [4. 3. 0]壬 -5-烯， 乙醇钾， 或甲醇钠， 优选含钠 碱如氢化钠存在下， 溶剂如四氢呋喃，醚溶剂， Ν,Ν-二甲基甲酰胺， 或二甲亚砜， 或两种 或多种前述溶剂的溷合物中， 在 0Ό〜约 60'C的温度范围内处理通式 IV化合物， 可得到 通式 V化合物。 In the first method (Method A), (CH 3 ) 3 S(0)X 2 wherein X 2 is halogen, -BF 4 , or -PF 6 wherein the halogen is preferably iodine, in a base such as tert-butyl Potassium alkoxide, sodium t-butoxide, sodium ethoxide, sodium hydride, 1,1,3,3-tetramethylguanidine, 1,8-diazabicyclo[5. 4. 0]undec-7-ene, 1 , 5-diazabicyclo[4.3.0]non-5-ene, potassium ethoxide, or sodium methoxide, preferably in the presence of a sodium base such as sodium hydride, a solvent such as tetrahydrofuran, an ether solvent, hydrazine, hydrazine-dimethyl The compound of the formula V can be obtained by treating the compound of the formula IV in a temperature range of from 0 Torr to about 60 ° C in a carboxamide, or dimethyl sulfoxide, or a mixture of two or more of the foregoing solvents.
在第二种方法 (方法 B)中， 用 (CH3)3SX2, 其中 X2是卤素， -BF4, 或 -PF6，优选是 -BF4, 在碱如叔丁醇钾， 叔丁醇钠， 乙醇钠， 氢化钠， 1,1,3,3-四甲基胍， 1，8-二氮杂双环[5. 4. 0] ^一 -7-烯， 1,5-二氮杂双环 [4.3.0]壬 -5-烯，乙醇钾，六甲基二硅氮垸钾 ((KHMDS)(potassium hexamethyldisilazide),或甲醇钠，优选 KHMDS存在下，在溶剂如四氢呋喃,醚溶剂， Ν,Ν- 二甲基甲酰胺， 或二甲亚砜， 或两种或多种前述溶别的混合物中， 在 -78'C〜约 60°C的温 度范围内处理通式 IV化合物， 可得到通式 V化合物。 In the second method (Method B), (CH 3 ) 3 SX 2 wherein X 2 is halogen, -BF 4 , or -PF 6 , preferably -BF 4 , in a base such as potassium t-butoxide, uncle Sodium butoxide, sodium ethoxide, sodium hydride, 1,1,3,3-tetramethylguanidine, 1,8-diazabicyclo[5. 4. 0] ^-7-ene, 1,5-di Azabicyclo[4.3.0]non-5-ene, potassium ethoxide, potassium hexamethyldisilazide (KHMDS), or sodium methoxide, preferably in the presence of KHMDS, in a solvent such as tetrahydrofuran, ether solvent , hydrazine, hydrazine-dimethylformamide, or dimethyl sulfoxide, or a mixture of two or more of the foregoing solvents, treating the compound of formula IV at a temperature ranging from -78 ° C to about 60 ° C, A compound of the formula V can be obtained.
在步骤 e中， 通式 V化合物可转换为其中 R2是羟基且 R3是以杂原子取代或未取代 的有机物，且所述杂原子为 ή素、 N、0和 S中的一种或多种；更为具体的是， R3为 -CH2R20, 其中 R2o为含 C、 H、 0、 N、 S和卤素中至少一种原子的有机或无机基团。 In the step e, the compound of the formula V can be converted into an organic substance in which R 2 is a hydroxyl group and R 3 is a hetero atom substituted or unsubstituted, and the hetero atom is one of halogen, N, 0 and S or More specifically; R 3 is -CH 2 R 20 , wherein R 2 o is an organic or inorganic group containing at least one of C, H, 0, N, S and halogen.
为了制备通式（I )中 R3的 -CH2R2()， 可用通式 HR2Q为原料， 在有或无极性的溶剂如 水、 甲醇、 四氢呋喃、 或其混合物中， 在约室温至约 100'C的温度范围内， 优选 60Ό , 任意在试剂如碘化钾， 高氯酸镁， 四氟硼酸锂， 吡啶盐酸盐或四垸基卤化铰卤化试剂如 四丁基溴化铵存在下，处理通式 V化合物，得通式（ I )化合物。所述方法在 R3为 -CH2NHR30 时尤其适用。 For the preparation of -CH 2 R 2 ( ) of R 3 in the formula (I), the formula HR 2Q can be used as a starting material, in a solvent having or without polarity such as water, methanol, tetrahydrofuran, or a mixture thereof, at about room temperature to about In the temperature range of 100 ° C, preferably 60 Ό, any treatment in the presence of a reagent such as potassium iodide, magnesium perchlorate, lithium tetrafluoroborate, pyridine hydrochloride or tetradecyl halogenated hinge halogenating reagent such as tetrabutylammonium bromide A compound of the formula V gives a compound of the formula (I). The process is especially useful when R 3 is -CH 2 NHR 30 .
为了制备通式（I )中 R3的 -CH2SR5()， 可用通式 HSR5o为原料， 在有或无极性溶剂如 水、 甲醇、 四氢呋喃、 或其混合物中， 在约室温至约 100'C的温度范围内， 优选 60'C， 任意在试剂如碘化钾， 高氯酸镁， 四氟硼酸锂， 吡啶盐酸盐或四垸基卤化铵卤化试剂如 四丁基溴化铵存在下， 处理通式 V化合物， 得通式（I )化合物 C-3-取代的 -9-脱氧 -9A-氮 杂 -9A-高红霉素 A衍生物。 For the preparation of -CH 2 SR 5( ) of R 3 in the general formula (I), the general formula HSR 5 o can be used as a starting material, in the presence or absence of a polar solvent such as water, methanol, tetrahydrofuran, or a mixture thereof, at about room temperature to about In the temperature range of 100'C, preferably 60'C, in the presence of a reagent such as potassium iodide, magnesium perchlorate, lithium tetrafluoroborate, pyridine hydrochloride or tetradecyl ammonium halide halogenating reagent such as tetrabutylammonium bromide The compound of the formula V is treated to give a compound of the formula (I) a C-3-substituted-9-deoxy-9A-aza-9A-homoerythromycin A derivative.
本发明中术语 "卤素"， 除非另有说明， 包括氟， 氯， 溴或碘。  The term "halogen" in the present invention includes, unless otherwise stated, fluorine, chlorine, bromine or iodine.
本发明中术语 "垅基"， 除非另有说明， 包括具有直链， 环状或支链或它们混合的饱 和单价烃残基。 应理解当指环状部分时， 在所述烃基中至少存在 3个碳原子。 这类环状 部分例如包括环丙基， 环丁基和环戊基。  The term "mercapto" in the present invention includes, unless otherwise stated, saturated monovalent hydrocarbon residues having a linear, cyclic or branched chain or a mixture thereof. It will be understood that when referring to the cyclic moiety, there are at least 3 carbon atoms in the hydrocarbyl group. Such cyclic moieties include, for example, cyclopropyl, cyclobutyl and cyclopentyl.
本发明中术语 "烷氧基"， 除非另有说明， 包括 -0-烷基， 其中烷基定义如上。  The term "alkoxy" in the present invention, unless otherwise specified, includes -0-alkyl, wherein alkyl is as defined above.
本发明中术语 "芳基"， 除非另有说明， 包括通过除去一个氢衍生自芳香烃的有机残 基， 如苯基或萘基。  The term "aryl" in the present invention includes, unless otherwise stated, an organic residue derived from an aromatic hydrocarbon by removal of a hydrogen such as a phenyl group or a naphthyl group.
本发明中术语 "5*20元杂芳基"， 除非另有说明， 包括含有 1个或多个分别选自 0， S 和 N的杂原子的芳番杂环基， 其中每个杂环基在环系中具有 5-20个原子。 合适的 5-20 元杂芳基的例子包括吡啶基， 呋喃基， 噻吩基， 吡唑基， （1，2,3)-和 (1,2,4)-***基， 吡嗪  The term "5*20-membered heteroaryl" in the present invention includes, unless otherwise stated, an aromatic heterocyclic group containing one or more hetero atoms each selected from 0, S and N, wherein each heterocyclic group It has 5-20 atoms in the ring system. Examples of suitable 5-20 membered heteroaryl groups include pyridinyl, furyl, thienyl, pyrazolyl, (1,2,3)- and (1,2,4)-triazolyl, pyrazine
22  twenty two
替换页 （细则第 26条) 基， 四唑基， 呋喃 ¾， 异恶唑基， 恶唑基， 吡咯基和噻唑基。 Replacement page (Article 26) Base, tetrazolyl, furan 3⁄4, isoxazolyl, oxazolyl, pyrrolyl and thiazolyl.
本发明的化合物可含有不对称碳原子并因此存在不同的对映体和非对映体形式。 可 使用本领域已知的方法， 按照各自物理化学上的不同将非对映体混合物分为单个的非对 映体，例如，用色谱或分级结晶。可通过将对映体混合物与合适的光学活性化合物 (例如， 醇)反应转化为非对映体混合物， 然后分开非对映体并转化 (例如， 水解)各个非对映体得 到相应的纯的对映体。 使用所有这些异构体， 包括非对映体混合物和纯的对映体， 都是 本发明的一部分。  The compounds of the invention may contain asymmetric carbon atoms and thus exist in different enantiomeric and diastereomeric forms. The mixture of diastereomers can be separated into individual diastereomers according to their respective physicochemical differences using methods known in the art, for example, by chromatography or fractional crystallization. Conversion of the enantiomeric mixture to a mixture of diastereomers by reaction with a suitable optically active compound (eg, an alcohol), followed by separation of the diastereomers and conversion (eg, hydrolysis) of the individual diastereomers affords the corresponding pure Enantiomer. The use of all such isomers, including mixtures of diastereomers and pure enantiomers, is part of the present invention.
本发明所述"治疗"， 除非另有说明， 包括使用本发明的组合物治疗或预防细菌感染或原 生动物感染。 本发明所述的 "细菌感染"和"原生动物感染"， 除非另有说明， 包括发生在哺乳 动物， 禽， 鱼的细菌 染和原生动物感染， 以及可通过使用抗生素如本发明的化合物给药治 疗和预防的细菌感染和原生动物感染的疾病。  "Treatment" as used herein, unless otherwise indicated, includes the use of a composition of the invention to treat or prevent a bacterial infection or a protozoal infection. "Bacterial infection" and "protozoal infection" as used herein, unless otherwise indicated, include bacterial infections and protozoal infections that occur in mammals, birds, fish, and can be administered by the use of antibiotics such as the compounds of the invention. Treatment and prevention of bacterial infections and diseases of protozoal infections.
优选地， 本发明 述的细菌感染和原生动物感染以及这些感染的疾病引起的人类疾病， 包括： 由致病性链球齒、 流感嗜血杆菌、 莫拉氏菌、 金黄色葡萄球菌、 军团菌、 放线杆菌、 支原体、 衣原体感染引起的肺炎、 气管、 支气管炎、 中耳炎、 窦炎、 扁桃体炎、 咽炎、 肾炎; 由致病性葡萄球菌、 链球菌、 棒状杆菌引起的发热、 皮肤和软组织感染、 脓肿、 骨髓炎； 由 致病性葡萄球菌、 肠球菌、 衣原体、 螺旋体、 支原体、 奈瑟氏球菌感染引起的尿道炎、 子宫 颈炎、 淋病感染、性传播疾病等泌尿生殖***疾病； 由布氏疏螺旋体感染引起的 Lyme疾病； 由沙眼衣原体， 淋病柰瑟氏球菌， 金黄色葡萄球菌， 肺炎链球菌， 化脓链球菌， 流感嗜血菌， 或李斯特氏菌属感染的结膜炎， 角膜炎和泪囊炎； 由空肠弯曲杆菌感染引起的胃肠炎或由幽 门螺杆菌感染的溃疡; 由 Crytosporiduum spp感染引起的肠内原生动物感染； 由绿色链球菌 感染的牙原性感染； 由百日咳博德特氏菌感染的顽固性咳嗽； 由产气荚膜梭菌或拟杆菌类感 染的气性坏疽； 由幽 I l螺杆菌或肺炎衣原体感染的动脉硬化。  Preferably, the bacterial infections and protozoal infections of the present invention and human diseases caused by diseases of these infections include: by pathogenic streptococci, Haemophilus influenzae, Moraxella, Staphylococcus aureus, Legionella, Actinobacilli, mycoplasma, chlamydia, pneumonia, bronchitis, otitis media, sinusitis, tonsillitis, pharyngitis, nephritis; fever, skin and soft tissue infections caused by pathogenic staphylococci, streptococci, coryneform bacteria, Abscess, osteomyelitis; urinary tract disease caused by pathogenic staphylococcus, enterococci, chlamydia, spirochete, mycoplasma, Neisseria infection, cervicitis, gonorrhea infection, sexually transmitted diseases, etc.; Lyme disease caused by spirochete infection; conjunctivitis caused by Chlamydia trachomatis, Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, or Listeria infection, keratitis and tears Bunionitis; gastroenteritis caused by Campylobacter jejuni infection or by secluded Ulcers infected with Helicobacter; Intestinal protozoal infections caused by Crytosporiduum spp infection; Orogenic infections infected with Streptococcus mutans; Intractable cough infected by B. pertussis; Clostridium perfringens or Gastrogen gangrene infected by Bacteroides; arteriosclerosis infected by Helicobacter pylori or Chlamydia pneumoniae.
优选地， 本发明所述的可被治疗和预防的动物细菌感染和原生动物感染以及涉及这些感 染的疾病包括下列疾病： 由溶血性巴氏杆菌、 多杀性巴氏杆菌、 牛支原体， 或博德特氏菌感 染引起的牛呼吸***疾病； 由大肠杆菌或原生动物类 （如球虫）感染引起的牛肠道疾病； 由 金黄色葡萄球菌、 乳虏链球菌、 无乳链球菌、 停乳链球菌、 克雷伯氏菌、 棒状杆菌属、 肠球 菌感染引起的奶牛乳腺炎； 由大肠杆菌感染引起的牛、 猪子宫炎； 由牛莫氏菌感染的牛传染 性结膜炎； 由原生动物（即 nesporium)感染引起的母牛早产流产； 由肺炎放线杆菌、 多杀性 巴氏杆菌、 嗜血杆菌、 支原体属感染引起的猪呼吸道疾病； 由原生动物 （如弓形体、 附红细 胞体） 感染引起的血液原虫病； 由大肠杆菌、 沙门氏菌、 螺旋体感染引起的猪肠道疾病； 由 猪丹毒杆菌、猪链球菌、炭疽杆菌感染引起的猪败血症、 皮肤炎症、关节肿胀坏死以及化脓； 由大肠杆菌感染引起的猫、 狗尿道感染； 由表皮葡萄球菌， 中间葡萄球菌， 凝固酶葡萄球菌 或多杀性巴氏杆菌感染引起的猫、狗皮肤和软组织感染； 由产碱杆菌属、拟杆菌属、梭菌属、 肠杆菌、 真杆菌属、 消化链球菌， 卟啉单胞菌、 普雷沃氏菌引起的狗、 猫牙齿或口腔感染等； 由大肠杆菌、 沙门氏龠、 魏氏梭菌感染引起的禽肠道疾病； 由大肠杆菌、 巴氏杆菌、 葡萄球 菌、链球菌感染引起的禽败血症、皮肤软组织及内脏实质器官及黏膜炎症； 由原生动物类（如 球虫、住白细胞原虫） 引起的原虫病； 由支原体、 嗜血杆菌、 大肠杆菌引起的呼吸***疾病。  Preferably, the bacterial infections and protozoal infections of the animals which can be treated and prevented according to the invention and diseases involving these infections include the following diseases: from the hemolytic Pasteurella, Pasteurella multocida, M. bovis, or Bo Bovine respiratory diseases caused by Deuterium infection; bovine intestinal diseases caused by infection with Escherichia coli or protozoa (such as coccidia); by Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, lactation Cow mastitis caused by Streptococcus, Klebsiella, Corynebacterium, Enterococcus infection; Bovine and swine metritis caused by E. coli infection; Bovine contagious conjunctivitis infected by M. bovis; Protozoa Premature abortion of cows caused by infection (ie nesporium); respiratory diseases of pigs caused by Actinobacillus pneumoniae, Pasteurella multocida, Haemophilus, Mycoplasma; Protozoa (eg Toxoplasma, Eperythrozoon) Blood protozoa caused by infection; porcine intestinal diseases caused by infection with Escherichia coli, Salmonella, and spirochetes; Swine sepsis caused by bacteria, Streptococcus suis, Bacillus anthracis infection, skin inflammation, swelling and necrosis of joints; suppuration; cat and dog urinary tract infection caused by E. coli infection; Staphylococcus epidermidis, Staphylococcus aureus, coagulase Staphylococcus or more Cat, dog skin and soft tissue infections caused by Pasteurella multocida infection; from Alcaligenes, Bacteroides, Clostridium, Enterobacter, Eubacteria, Streptococcus pneumoniae, Porphyromonas, Prevo Dogs, cat teeth or oral infections caused by bacteria; poultry intestinal diseases caused by Escherichia coli, Salmonella, Clostridium welchii infection; Poultry caused by Escherichia coli, Pasteurella, Staphylococcus, Streptococcus infection Sepsis, skin soft tissue and visceral parenchymal organs and mucosal inflammation; protozoal diseases caused by protozoa (such as coccidia, living leukocyte protozoa); respiratory diseases caused by mycoplasma, Haemophilus, Escherichia coli.
23  twenty three
替换页 （细则第 26条) 本发明所述的有效剂量的治疗剂量， 单次给药为 2-50mg/kg, 优选 10mg/kg。 Replacement page (Article 26) The therapeutic dose of the effective dose of the present invention is 2-50 mg/kg, preferably 10 mg/kg, in a single administration.
本发明所述的 "药学上可接受的盐"， 除非另有说明， 包括可存在于本发明化合物中的酸 或碱基的盐。 性质上碱性的本发明化合物可与各种无机或有机酸形成盐。 可用于制备本发明 碱性化合物的药学上可接受的酸， 包括无机酸或有机酸， 如本发明的甲酸盐， 乙酸盐， 丙酸 盐， 乳酸盐， 柠檬酸盐， 酒石酸盐， 草酸盐， 苹果酸盐， 盐酸盐， 硫酸盐， 硝酸盐， 硫酸氢 盐， 磷酸盐， 酸式憐酸盐， 烟酸盐， 水杨酸盐， 泛酸盐， 抗坏血酸盐， 琥珀酸盐， 马来酸盐， 龙胆酸盐， 富马酸盐， 葡糖酸盐， 葡糖二酸盐， 蔗糖盐， 苯甲酸盐， 谷氨酸盐， 甲磺酸盐， 乙磺酸盐， 苯磺酸盐, 对甲苯磺酸盐以及各种氨基酸。 性质上是酸性的本发明化合物可与各 种药学上可接受的阳离子形成碱性盐。 这些盐包括碱金属和碱土金属， 如钙， 镁， 钠， 钾等。  The "pharmaceutically acceptable salts" of the present invention include, unless otherwise stated, salts of acids or bases which may be present in the compounds of the invention. The compounds of the invention which are basic in nature can form salts with various inorganic or organic acids. A pharmaceutically acceptable acid useful in the preparation of a basic compound of the invention, including inorganic or organic acids, such as formate, acetate, propionate, lactate, citrate, tartrate, Oxalate, malate, hydrochloride, sulphate, nitrate, bisulfate, phosphate, acid salt, nicotinate, salicylate, pantothenate, ascorbate, succinate , maleate, gentisate, fumarate, gluconate, gluconate, sucrose, benzoate, glutamate, methanesulfonate, ethanesulfonate, Toluenesulfonate, p-toluenesulfonate and various amino acids. The compounds of the invention which are acidic in nature form basic salts with various pharmaceutically acceptable cations. These salts include alkali metals and alkaline earth metals such as calcium, magnesium, sodium, potassium and the like.
本发明用于治疗哺乳动物、 禽、 鱼细菌感染或原生动物感染的药物组合物， 包括含有通 式（ I )的化合物或药学上可接受的盐作为活性成分， 和药学上可接受的载体。 所述药学上可 接受的载体是指任何可用于药学领域的稀释剂、 辅助剂。  The pharmaceutical composition for treating a mammalian, avian or fish bacterial infection or a protozoan infection of the present invention comprises a compound containing the general formula (I) or a pharmaceutically acceptable salt as an active ingredient, and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier means any diluent or adjuvant which can be used in the pharmaceutical field.
本发明的药物组合物的剂型为口服制剂， 注射剂， 外用制剂。  The pharmaceutical composition of the present invention is in the form of an oral preparation, an injection, or an external preparation.
优选地， 本发明的口服制剂为粉剂， 片剂， 胶囊剂， 颗粒剂， 溶液剂， 混悬剂。 注射剂 为粉针剂， 乳剂， 混晕剂， 溶液剂； 外用制剂为软膏剂， 滴剂。  Preferably, the oral preparation of the present invention is a powder, a tablet, a capsule, a granule, a solution, a suspension. The injection is a powder injection, an emulsion, a coagulant, a solution; the external preparation is an ointment, a drop.
本发明药物组合物中的载体是指药学领域组成制剂所必须的辅助成分， 包括： 稀释剂、 助溶剂、 抗氧化剂、 矫味剂、 防腐剂、 赋形剂、 凝结剂。  The carrier in the pharmaceutical composition of the present invention refers to an auxiliary component necessary for the formulation of the pharmaceutical composition, and includes: a diluent, a solubilizer, an antioxidant, a flavoring agent, a preservative, an excipient, and a coagulating agent.
具体实施方式 Detailed ways
下列提供的实施例说明了本发明的具体实施方案， 但本发明不限于下述实施例的范围。 衍生物核磁共振氢谱用 Bruker ARX-400测定， 质谱用 LCQ Series LC/MS测定； 高效液相用 Waters超高效液相色谱（UPLC) ACQUITY检测，所用原料及试剂除主要试剂已标出厂家及 批号其余均为市售分析纯或化学纯。 硅胶柱和薄层色谱所用溶剂比例除非另有说明按照本领 域技术人员理解均为体积比。  The examples provided below illustrate specific embodiments of the invention, but the invention is not limited to the scope of the following examples. The derivative nuclear magnetic resonance spectrum was measured by Bruker ARX-400, and the mass spectrum was determined by LCQ Series LC/MS. The high performance liquid phase was detected by Waters ultra performance liquid chromatography (UPLC) ACQUITY. The raw materials and reagents used were labeled with the main reagents and The rest of the batch numbers are commercially available analytically pure or chemically pure. The solvent ratios used in the silica gel column and thin layer chromatography are all volume ratios as understood by those skilled in the art unless otherwise stated.
下面为本  Below
Figure imgf000025_0001
Figure imgf000025_0001
化合物 1 化合物 2  Compound 1 compound 2
24  twenty four
替换页 （细则第 26条) Replacement page (Article 26)
Figure imgf000026_0001
Figure imgf000026_0001
Figure imgf000026_0002
Figure imgf000026_0002
通式 I  Formula I
实施例 1 Example 1
本实施例目的是制备上述通式 2的化合物， 该化合物名为： （2 38，411，51 ,811, 101 , 11R, The purpose of this example is to prepare a compound of the above formula 2, which is named (2 38,411,51,811,101, 11R,
128，138,141 )-13-[(2，6-二脱氧-3-。-甲基-3-0-甲基-(1 -己吡喃核糖基-氧基] -2-乙基 -3，4，10-三 羟基 -3，5，8，10,12,14-六甲基 -11-[[3，4，6-三脱氧 -3- (二甲基氨基 )-2-0- [(苯基甲氧基)羰基] -β-己卩比 喃木糖基]氧基] -1-氧杂 -6-氮杂环十五垸 -15-酮。 128,138,141 )-13-[(2,6-dideoxy-3-.-methyl-3-0-methyl-(1-hexylapyranosyl-oxy)-2-ethyl-3, 4,10-trihydroxy-3,5,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-2-0- [ (Phenylmethoxy)carbonyl]-β-hexamylpyroxypyranyl]oxy]-1-oxa-6-azacyclopentadecane-15-one.
在 2L三口反应瓶中加 800mL二氯甲垸， 冷至 0-5 'C , 搅拌， 加入 50g (0.068moL)化 合物 1 (国邦进出口公司生产， 批号： 20091101 ) ， 搅拌至溶解。 取氯甲酸苄酯（新沂市汇 力精细化工公司， 批号： 20111008) 28.8g (24mL; 0.應 moL) 溶到 60mL二氯甲垸中， 恒 压滴入， 控制温度在 0-5°C。 滴毕， 此温度下搅拌 lh， 反应毕 50'C减压旋蒸浓缩至干， 得到 浅黄色固体 50g化合物 2, 收率： 84.57%。  Add 800 mL of methylene chloride to a 2 L three-neck reaction flask, cool to 0-5 'C, stir, add 50 g (0.068 moL) of compound 1 (manufactured by Guobang Import and Export Co., Ltd., batch number: 20091101), stir until dissolved. Take benzyl chloroformate (Xinyi Huili Fine Chemical Co., Ltd., batch number: 20111008) 28.8g (24mL; 0. should be moL) dissolved in 60mL of dichloromethane, constant pressure drop, control temperature is 0-5° C. After completion of the dropwise addition, the mixture was stirred at this temperature for 1 hour, and the mixture was evaporated to dryness under reduced pressure of 50 <0>C to give pale yellow solid 50 g Compound 2, yield: 84.57%.
HPLC测定纯度： ≥98%。 （应用 WATERS ACQUITY UPLC BEH C18色谱柱 (2.1x50mm， 1.7μιη); 流动相为乙腈 -0.01moL/L乙酸铵 （55:45 ) ； 流速 0.20mL/min, 保留时间 4.27min; 检测波长 210nm; 柱溫 40°C， 进样量 2.5μ1。 ) Purity by HPLC: ≥98%. (Applying WATERS ACQUITY UPLC BEH C 18 column (2.1x50mm, 1.7μιη) ; mobile phase is acetonitrile-0.01moL/L ammonium acetate (55:45); flow rate 0.20mL/min, retention time 4.27min; detection wavelength 210nm; The column temperature is 40 ° C and the injection volume is 2.5 μ1.)
薄层色谱 TLC ¾=0.65(二氯甲烷： 甲醇 =7:1)  Thin layer chromatography TLC 3⁄4 = 0.65 (dichloromethane: methanol = 7:1)
1H-NMR(400MHz) δ : 7.32-7.39 ( m，5H ) , 4.99-5.18(m,3H), 4.38-4.40(d,lH =8Hz), 1 H-NMR (400 MHz) δ : 7.32-7.39 (m, 5H), 4.99-5.18 (m, 3H), 4.38-4.40 (d, lH = 8 Hz),
25  25
替换页 （细则第 26条） 4.16(s, 1 H),4.09-4.14(m,3H),3.94(s,2H), 3.50-3.52(m,2H), 3.30-3.33(m,4H), 3.22(s,3H), 2.91-3.02(m,3H), 2.28-2.50(m,4H), 2.21(s,6H),1.43-1.60(m,10H), 1.02-1.15(m,23H), 0.77-0.99(m,6H). Replacement page (Article 26) 4.16(s, 1 H), 4.09-4.14 (m, 3H), 3.94 (s, 2H), 3.50-3.52 (m, 2H), 3.30-3.33 (m, 4H), 3.22 (s, 3H), 2.91 -3.02 (m, 3H), 2.28-2.50 (m, 4H), 2.21 (s, 6H), 1.43-1.60 (m, 10H), 1.02-1.15 (m, 23H), 0.77-0.99 (m, 6H) .
ESI/MS: m/z 86 M+H]十。  ESI/MS: m/z 86 M+H] ten.
实施例 2 Example 2
本实施例目的是制备上述通式 3的化合物， 该化合物名为： （2R，3S，4R,5R，8R， 10R, 11R, 12S,13S,14R)-2-乙基 -3,4,10,13-四羟基 -3，5,8,10，12，14-六甲基 -11-[[3，4，6-三脱氧 -3- (二甲基氨 基) -2-0- [(苯基甲氧基)豫基] -β-己吡喃木糖基]氧基]小氧杂 -6-氮杂环十五垸 -15-酮。  The purpose of this example is to prepare a compound of the above formula 3, which is named: (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-2-ethyl-3, 4, 10 ,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-2-0- [( Phenylmethoxy)-hetero]-β-hexyranopyranosyl]oxy]oxyx-6-azacyclopentadecane-15-one.
在 5L三颈瓶中加入 95%乙醇 1L， 于水浴锅中 50。C下加热搅拌， 称取 300 g(0.345moL) 用实施例 1法制备的化合物 2， 再取 95%乙醇 1L加入反应瓶中， 搅拌溶解； 取浓盐酸 750 mL(9.0moL)于 1800mL水中搅拌混匀， 分批加入反应液中。 50Ό反应 22h。 反应毕， 冷至室 温，依次使用叔丁基申醚 (4000mLx3)萃取，得下层水相，再取碳酸钠 610g溶于 4000mL水中， 搅拌溶解后， 剧烈搅拌下缓缓加入上述萃取所得的水相中， 搅拌 0.5h。 反应完毕， 向上述水 相中加入乙酸异丙酯 (6000mLx3)萃取有机相， 合并有机相，加活性炭脱色 0.5h，滤除活性炭。 对所得有机相减压浓缩至干， 得白色固体 220.8g化合物 3。 收率： 93.9% ； HPLC测定纯度： 91°/。。 （应用 WATERS ACQUITY UPLC BEH C18色谱柱 (2.1 <50mm， 1.7μηι); 流动相为乙腈 -0.01moL/L乙酸铵 （55:45 ) ； 流速 0.20mL/min， 保留时间 2.95min; 检测波长 210nm; 柱温 40°C， 进样量 2.5μ1。 )  Add 1 L of 95% ethanol to a 5 L three-necked flask in a water bath 50. Heat and stir under C, weigh 300 g (0.345 moL) of compound 2 prepared by the method of Example 1, and then add 1 L of 95% ethanol to the reaction flask, and stir to dissolve; 750 mL (9.0 moL) of concentrated hydrochloric acid was stirred in 1800 mL of water. Mix and add to the reaction mixture in portions. 50Ό reaction 22h. After completion of the reaction, the mixture was cooled to room temperature, and then extracted with tert-butyl ether (4000 mL×3) to obtain the lower aqueous phase. Then, 610 g of sodium carbonate was dissolved in 4000 mL of water, stirred and dissolved, and the aqueous phase obtained by the above extraction was slowly added under vigorous stirring. Medium, stirring for 0.5 h. After completion of the reaction, the organic phase was extracted by adding isopropyl acetate (6000 mL x 3) to the above aqueous phase, and the organic phase was combined, decolorized by adding activated carbon for 0.5 h, and activated carbon was filtered off. The obtained organic phase was concentrated to dryness under reduced pressure to yieldd white crystals (yel. Yield: 93.9%; HPLC purity: 91 ° /. . (Apply WATERS ACQUITY UPLC BEH C18 column (2.1 <50mm, 1.7μηι); mobile phase is acetonitrile-0.01moL/L ammonium acetate (55:45); flow rate 0.20mL/min, retention time 2.95min; detection wavelength 210nm; The column temperature is 40 ° C and the injection volume is 2.5 μ1.)
TLC RiND.45(二氯甲烷： 甲醇 =7:1)  TLC RiND.45 (dichloromethane: methanol = 7:1)
13C-NMR(400MHtz) δ ： 175.3(15-0-C=0)； 154.2(2'-0-C=0);135.8 (C-5-2，-苯环 -1位1 3 C-NMR (400 MHtz) δ : 175.3 (15-0-C=0); 154.2 (2'-0-C=0); 135.8 (C-5-2, -benzene ring-1 position
C);128.3(苯环 -4位 C);128.2(苯环 -2， 6位 2C); 128.1(苯环 -3, 5位 C); 128.3 (benzene ring - 4 position C); 128.2 (benzene ring -2, 6 position 2C); 128.1 (benzene ring -3, 5 position
2C);97.9(C-6-O-l '-C) ;84.2(C-2');76.1 ;75.4;74.7;72.8;72.3;68.4;67.8;62.3;57.3;43.0;40.3;40.2;40.0 ;39.8(3'-NMe2),39.5;39 2;38.9;38.7;35.2;30.4;28.6;26.2;21.36;20.9;20.3;17.0;16.5;13.2;10.4;7.7 1H-NMR(400MHz) δ: 7.27-7.40 (m,5H) , 5.10-5.25(m,3H), 4.69-4.71(d,lH =8Hz), 4.60(s,lH)，4.56-4.60(m，3H),3.64(s，lH)， 3.50-3.52(m,lH), 3.29-3.35(m,lH), 3.18(s,3H), 2C); 97.9 (C-6-Ol '-C); 84.2 (C-2');76.1;75.4;74.7;72.8;72.3;68.4;67.8;62.3;57.3;43.0;40.3;40.2;40.0;(3'-NMe 2 ), 39.5; 39 2; 38.9; 38.7; 35.2; 30.4; 28.6; 26.2; 21.36; 20.9; 20.3; 17.0; 16.5; 13.2; 10.4; 7.7 1H-NMR (400 MHz) δ: 7.27- 7.40 (m,5H) , 5.10-5.25(m,3H), 4.69-4.71(d,lH=8Hz), 4.60(s,lH),4.56-4.60(m,3H),3.64(s,lH), 3.50-3.52(m,lH), 3.29-3.35(m,lH), 3.18(s,3H),
2.52-2.75(m,3H), 2.26-2.49 (m，4H), 1.71-1.92(m,4H), 1.40- 1.67(m,6H), 1.02-1.15(m,20H), 2.52-2.75 (m, 3H), 2.26-2.49 (m, 4H), 1.71-1.92 (m, 4H), 1.40- 1.67 (m, 6H), 1.02-1.15 (m, 20H),
0.77-0.99(m,6H). 0.77-0.99 (m, 6H).
ESI/MS: m/z 711.07 [M+H]十。  ESI/MS: m/z 711.07 [M+H] ten.
实施例 3 Example 3
本实施例目的是制备上述通式 4的化合物， 该化合物名为： （21 ,38,41^511,81， 1 OR, 11 R, The purpose of this example is to prepare a compound of the above formula 4, which is named (21, 38, 41^511, 81, 1 OR, 11 R,
12S,13S,14R)-2-乙基 -3,4,10 -三羟基 -3，5，8，10，12，14-六甲基 -11-[[3,4,6-三脱氧 -3- (二甲基氨 基) -2-0- [(苯基甲氧基)羰基] -β-己吡喃木糖基]氧基] -1-氧杂 -6-氮杂环十五垸 -13， 15二酮。 二甲亚砜 /三氟乙酸酑氧化 12S,13S,14R)-2-ethyl-3,4,10-trihydroxy-3,5,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy- 3-(Dimethylamino)-2-0-[(phenylmethoxy)carbonyl]-β-hexyranopyranyl]oxy]-1-oxa-6-azacyclopentadecane -13, 15 diketone. Dimethyl sulfoxide / trifluoroacetic acid hydrazine oxidation
氮气保护下将 10g (0.014moL)化合物 3加入到 60mL二氯甲垸中， 搅泮， 冷却至 0'C左 右， 力 t] 22.0mL二甲 ¾砜（成都市科隆化工公司， 批号： 20100708)， 然后取 4.6mL三氟乙酸 酐（江苏石堰化工公司， 批号： 20101008)滴加， 滴加完毕后反应 30min, 滴加 9.8mL三乙  Under nitrogen protection, 10g (0.014mL) of compound 3 was added to 60mL of dichloromethane, stirred and cooled to about 0'C, force t] 22.0mL of dimethyl 3⁄4 sulfone (Chengdu Cologne Chemical Company, Lot No.: 20100708) Then, 4.6mL of trifluoroacetic anhydride (Jiangsu Shiqi Chemical Co., Ltd., batch number: 20101008) was added dropwise. After the addition was completed, the reaction was carried out for 30 minutes, and 9.8 mL of triethyl was added dropwise.
26  26
替换页 （细则第 26条) 胺（成都市科隆化工公司， 批号： 20100708)， 内温控在 -60'C〜- 65°C， 搅拌反应 0.5h。完毕， 停止反应， 升至室温。 而后向反应液中加入 70mL水， 萃取分得有机相， 有机相再用 50mL 饱和碳酸氢钠溶液洗涤一次， 分层得有机相， 有机相再用 70mL水洗涤， 然后向有机相中加 入 4.0g无水硫酸镁干燥。滤除无水硫酸镁， 得浅黄色滤液， 滤液减压浓缩至干得到 8.2g化合 物 4。收率： 82.2% ； HPLC测定纯度： 91%。（应用 HPLC-Waters Symmetry C8, 15cm x 3.9mm I.D.柱， 以甲醇： 醋酸铵 (25:75)为流动相， 流速 2.0mL/min， 保留时间 5.07min)。 Replacement page (Article 26) Amine (Chengdu Cologne Chemical Company, batch number: 20100708), internal temperature control at -60'C~-65 °C, stirring reaction for 0.5h. When finished, stop the reaction and raise to room temperature. Then, 70 mL of water was added to the reaction solution, and the organic phase was extracted. The organic phase was washed once more with 50 mL of saturated sodium hydrogen carbonate solution, and the organic phase was separated. The organic phase was washed with 70 mL of water, and then 4.0 g was added to the organic phase. Dry over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was filtered off to give a pale yellow filtrate. Yield: 82.2%; HPLC purity: 91%. (HPLC-Waters Symmetry C8, 15 cm x 3.9 mm ID column, methanol: ammonium acetate (25:75) as mobile phase, flow rate 2.0 mL/min, retention time 5.07 min).
方法 2 Method 2
采用 N-氯丁二酰亚胺 /二甲硫醚来氧化 Oxidation with N-chlorosuccinimide / dimethyl sulfide
于 5L三颈瓶中加 57.9g, 0.42moLN-氯丁二酰亚胺（大中原联合化学（郑州）有限公司， 批号： 201005 )加于无水 600mL二氯甲垸， 移于低温槽中搅拌降温至 -20 °C， 滴加甲硫醚（阿 拉丁试剂（上海）有限公司）（36mL， 0.49moL), 控温搅拌 30min。 滴加通式化合物 3( 220 g， 0.31moL)的二氯甲垸 (1200mL)溶液， 搅拌 30min， 反应毕， 反应液依次用饱和碳酸氢钠， 饱 和食盐水，鶴，得有机相，无水硫酸镁干燥，减压下蒸除溶剂得白色固体 184.2g (收率 84%) 化合物 4。 HPLC测定纯度： 91%。 （应用 HPLC-Waters Symmetry C8, 15cm X 3.9mm I.D.柱， 以甲醇： 醋酸铵 (25:75)为流动相， 流速 2.0mL/min， 保留时间 5.07min)。  Add 57.9g, 0.42moLN-chlorosuccinimide (Dazhongyuan United Chemical (Zhengzhou) Co., Ltd., batch number: 201005) to 5L three-necked flask, add 600mL of dichloromethane to anhydrous, and transfer to the low temperature tank for stirring. The temperature was lowered to -20 ° C, and methyl sulfide (Aladdin Reagent (Shanghai) Co., Ltd.) (36 mL, 0.49 mol) was added dropwise, and the mixture was stirred under controlled temperature for 30 min. A solution of the compound of formula 3 (220 g, 0.31 mol) in dichloromethane (1200 mL) was added dropwise and stirred for 30 min. After the reaction was completed, the reaction mixture was washed with saturated sodium hydrogen carbonate, brine, After drying over magnesium sulfate, the solvent was evaporated under reduced pressure to give 184.2 g (yield: 84%) Compound 4. Purity by HPLC: 91%. (HPLC-Waters Symmetry C8, 15 cm X 3.9 mm I.D. column, methanol: ammonium acetate (25:75) as mobile phase, flow rate 2.0 mL/min, retention time 5.07 min).
方法 3 Method 3
改良 Pritzner-Moffatt氧化方法 (二甲亚砜 EDC-HC1/三氟乙酸-吡啶） Modified Pritzner-Moffatt oxidation method (dimethyl sulfoxide EDC-HC1/trifluoroacetic acid-pyridine)
将化合物 3(7.00 g， 10.0 mmOl)和 1-乙基 -(3-二甲基氨基丙基)碳酰二亚胺盐酸盐 (EDC'HCl) (苏州昊帆生物科技有限公司； 批号： 20110608) (2.9g, 15.13 mmoL)加入到二氯甲垸 (75mL) 中， 搅泮， 冷却至 0°C左右， 滴加二甲亚砜 (14.0mL， 197.3mmoL), 然后加入三氟乙酸吡啶盐 (参考杨红文.化学研究与应用.2000.12(1):74-76自制； 批号： 20110408)2.9g， 15.02 mmoL)的二 氯甲垸 (15.0 mL)溶液， 控制温度不超过 3'C， 滴加完毕后在该温度下继续搅拌反应 6〜8 h， 反应完全后加入水 (50.0mL)搅拌 0.5 h， 静置分层， 有机层再用 20 mL水洗涤， 无水硫酸镁干 燥， 过滤， 滤液减压浓缩得化合物 46.1g固体 (收率 87.4%)。 HPLC测定纯度： 91%。 （应用 WATERS ACQUITY UPLC BEH C18色谱柱 (2.1x50mm， 1.7μιη);流动相为乙腈 -0.01moL/L乙酸 铵（55:45 );流速 0.20mL/min，保留时间 3.01min;检测波长 210nm;柱温 40'C，进样量 2.5μ1。） TLC ¾=0.55(二氯甲垸： 甲醇 =7:1) Compound 3 (7.00 g, 10.0 mmOl) and 1-ethyl-(3-dimethylaminopropyl)carbonyldiimide hydrochloride (EDC'HCl) (Suzhou Yifan Biotechnology Co., Ltd.; batch number: 20110608) (2.9g, 15.13 mmoL) was added to dichloromethane (75mL), stirred, cooled to about 0 ° C, dimethyl sulfoxide (14.0 mL, 197.3 mmoL) was added dropwise, then pyridine trifluoroacetate was added. Salt (refer to Yang Hongwen. Chemical Research and Application. 2000.12 (1): 74-76 homemade; batch number: 20110408) 2.9g, 15.02 mmoL) solution of methylene chloride (15.0 mL), control temperature does not exceed 3'C, drop After the addition is completed, the reaction is further stirred at this temperature for 6-8 h. After the reaction is completed, water (50.0 mL) is added and stirred for 0.5 h, and the mixture is allowed to stand for separation. The organic layer is washed with 20 mL of water, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to give compound 46.1 g (yield: 87.4%). Purity by HPLC: 91%. (Applying WATERS ACQUITY UPLC BEH C 18 column (2.1x50mm, 1.7μιη); mobile phase is acetonitrile-0.01moL/L ammonium acetate (55:45); flow rate 0.20mL/min, retention time 3.01min; detection wavelength 210nm; The column temperature is 40'C and the injection volume is 2.5μ1.) TLC 3⁄4=0.55 (dichloroformamidine: methanol = 7:1)
13C-NMR(400MHz) 6 ： 211.3(3-^=0) 172.3(15-0-£=0)； 151.5(2，-O-£=O);140.9(C-5-2，-苯 环 -1C);128.3(苯环 -4 位 C);128.2(苯环 -2， 6 位 2C); 128.1(苯环 -3,5 位 2C);97.9(C-6-0-l'- C) ;84.2(C-2');76.1;75.4;74.7;72.8;72.3;68.4;67.8;62.3;57.3;43.0;40.3;40.2;40.0;39.8(3'-NMe2),39.5 ;39.2;38.9;38.7;35.2;30.4;28.6;26.2;21.36;20.9;20.3;17.0;16.5;13.2;10.4;7.7 13 C-NMR (400MHz) 6 : 211.3 (3-^ = 0) 172.3 (15-0 - £ = 0); 151.5 (2, -O-£=O); 140.9 (C-5-2, -benzene Ring-1C); 128.3 (benzene ring-4 position C); 128.2 (benzene ring-2, 6 position 2C); 128.1 (benzene ring-3, 5 position 2C); 97.9 (C-6-0-l'- C); 84.2 (C-2');76.1;75.4;74.7;72.8;72.3;68.4;67.8;62.3;57.3;43.0;40.3;40.2;40.0; 39.8 (3'-NMe 2 ), 39.5; 38.9;38.7;35.2;30.4;28.6;26.2;21.36;20.9;20.3;17.0;16.5;13.2;10.4;7.7
1H-NMR(400MHz) δ： 7.34-7.53 ( m,5H ) , 5.39-5.41(m,3H), 5.06-5.07(d,lH =4Hz), 4.76(s,lH),4.58-4.62(m,3H), 3.38-3.49(m,lH), 3.15(s,3H), 2.55-2.63(m,3H), 2.28-2.48 (m，4H)， 1.72- 1.94(m,4H), 1.32-1.65(m,6H), 1.02-1.25(m,20H), 0.73-0.96(m,6H). 1H-NMR (400MHz) δ: 7.34-7.53 (m, 5H), 5.39-5.41 (m, 3H), 5.06-5.07 (d, lH = 4Hz), 4.76 (s, lH), 4.58-4.62 (m, 3H), 3.38-3.49 (m, lH), 3.15 (s, 3H), 2.55-2.63 (m, 3H), 2.28-2.48 (m, 4H), 1.72- 1.94 (m, 4H), 1.32-1.65 ( m, 6H), 1.02-1.25 (m, 20H), 0.73-0.96 (m, 6H).
ESI/MS: m/z 709.18 [M+H]十。  ESI/MS: m/z 709.18 [M+H] dec.
实施例 4 Example 4
本实施例目的是制备上述通式 5的化合物， 该化合物名为： （4R,7R,8S,9R，10R,13R， 15R,  The purpose of this example is to prepare a compound of the above formula 5, which is named: (4R, 7R, 8S, 9R, 10R, 13R, 15R,
. . 27 一. . . 27 one.
替换页 （细则第 26条) l6R, l7S)-l6-[[3,4,6-三脱氧 _3_ (二甲基氨基 )-2-0- [(苯基甲氧基)羰基] -β-己吡喃木糖基]氧基] -7- 乙基 -8,9,15-三羟基 "4,8,10,13,15,17-六甲基 -1，6-二氧 -11-氮杂 -嫘环 [2.14]十七垸 -5-酮（结构式如 下， 下同） 。 Replacement page (Article 26) l 6 R, l 7 S)-l 6 -[[ 3 , 4 , 6 -Trideoxy_ 3 _ (dimethylamino)-2-0-[(phenylmethoxy)carbonyl]-β-hexyl Pyranopyranyl]oxy]-7-ethyl-8,9,15-trihydroxy"4,8,10,13,15,17-hexamethyl-1,6-dioxo-11-nitrogen Hetero-anthracene ring [2.14] heptadec-5-one (structure is as follows, the same below).
Figure imgf000029_0001
于 3L三颈瓶中加入 120g三甲基溴化硫（(Me)3SBr) (宁波应发硼纳有限公司)和 lOOOmL 四 氢呋喃， -5~0°C搅拌加入 120g叔丁醇钾 (山东德州龙腾纺织浆料有限公司；批号： 201101206), 控温搅拌 15min， 通氮气， 降温至 -70°C。 维持低温 -70°C , 滴加化合物 4 (300g， 0.42moL) 的 二氯甲垸溶液于 -65〜- 60°C反应， 自开始滴加计时搅拌 3h， ¾N2保护。 反应结束加氯化铵溶 液 (130g氯化铵加 720mL纯化水)， 内温至 5〜10°C，搅拌 15min，静置分层，水层用 200mL二 氯甲烷萃取一次， 合并有机相。 有机相水 （200mLx4)洗， 得有机相， 无水硫酸镁干燥， 过 滤， 滤液 60Ό减压浓缩成粘稠溶液。得化合物 5。该粘稠液可直接用于下步反应。 HPLC测定 纯度： 89%。 （应用 WATERS ACQUITY UPLC BEH C18色谱柱 (2.1 x50mm， 1.7μηι); 流动相为 乙腈 -0.01moL/L乙酸铵 （55:45 ) ； 流速 0.20mL/min， 保留时间 3.77min; 检测波长 210nm; 柱 温 40°C， 进样量 2.5μ1。 )
Figure imgf000029_0001
Add 3 g of trimethyl sulfide ((Me) 3 SBr) (Ningbo Yingfa Born Co., Ltd.) and 1000 mL of tetrahydrofuran to a 3 L three-necked flask, and add 120 g of potassium t-butoxide with stirring at -5~0 °C (Dongzhou, Shandong) Longteng Textile Slurry Co., Ltd.; batch number: 201101206), temperature controlled stirring for 15min, nitrogen gas, cooling to -70 °C. While maintaining the low temperature at -70 ° C, a solution of the compound 4 (300 g, 0.42 mol) of dichloromethane was added dropwise at -65 to -60 ° C, and the mixture was stirred for 3 h from the start of the dropwise addition, and protected by 3⁄4 N 2 . At the end of the reaction, an ammonium chloride solution (130 g of ammonium chloride plus 720 mL of purified water) was added, the internal temperature was adjusted to 5 to 10 ° C, stirred for 15 min, and the mixture was allowed to stand for separation. The aqueous layer was extracted once with 200 mL of dichloromethane, and the organic phases were combined. The organic phase was washed with water (200 mL×4), and then evaporated and evaporated. Compound 5 was obtained. The viscous liquid can be used directly in the next step of the reaction. Purity by HPLC: 89%. (Apply WATERS ACQUITY UPLC BEH C18 column (2.1 x 50mm, 1.7μηι); mobile phase acetonitrile-0.01moL/L ammonium acetate (55:45); flow rate 0.20mL/min, retention time 3.77min; detection wavelength 210nm; Temperature 40 ° C, injection volume 2.5μ1.)
13C-NMR(400MHz) 5 ： 176.5(15-0-C=0) ； 154.7(2'-0-C=0);135.6(C-5-2'-苯环1 3 C-NMR (400MHz) 5 : 176.5 (15-0-C=0); 154.7 (2'-0-C=0); 135.6 (C-5-2'-benzene ring
-1C);128.4(苯环 -4 位 C);128.4(苯环 -2， 6 位 2C); 127.4(苯环 -3，5 位 2C);94.5(C-6-0-l'- C) ;84.2(C-2');76.1;75.4;74.7;72.8;72.3;68.4;67.8;62.3;57.3;49.6;43.0;40.3;40.2;40.0;39.8(3'-NMe2) ,39.5;39.2;38.9;38.7;35.2;30.4;28.6;26.2;21.36;20.9;20.3;17.0;16.5;13.2;10.4;7.7 -1C); 128.4 (benzene ring-4 position C); 128.4 (benzene ring-2, 6 position 2C); 127.4 (benzene ring-3, 5 position 2C); 94.5 (C-6-0-l'-C ;84.2(C-2');76.1;75.4;74.7;72.8;72.3;68.4;67.8;62.3;57.3;49.6;43.0;40.3;40.2;40.0;39.8(3'-NMe 2 ) ,39.5;39.2 ;38.9;38.7;35.2;30.4;28.6;26.2;21.36;20.9;20.3;17.0;16.5;13.2;10.4;7.7
1H-NMR(400MHz) 6: 7.35-7.39 (m,5H) , 5.14-5.27(m,3H),
Figure imgf000029_0002
 1 H-NMR (400 MHz) 6: 7.35-7.39 (m, 5H), 5.14-5.27 (m, 3H),
Figure imgf000029_0002
4.86(s,lH),4.52-4.63(m,3H), 3.32-3.4l(m,lH), 3.18(s,3H), 2.58-2.82(m,2H), 2.55-2.63(m,3H), 2.26-2.48 (m,4H), 1.74-1.98(m,4H), 1.35- 1.67(m,6H), 1.03-1.25(m,20H), 0.72-0.96(m,6H). 4.86(s,lH), 4.52-4.63(m,3H), 3.32-3.4l(m,lH), 3.18(s,3H), 2.58-2.82(m,2H), 2.55-2.63(m,3H) , 2.26-2.48 (m, 4H), 1.74-1.98 (m, 4H), 1.35- 1.67 (m, 6H), 1.03-1.25 (m, 20H), 0.72-0.96 (m, 6H).
TLC ¾=0.55(二氯甲垸： 甲醇 =8:1)  TLC 3⁄4 = 0.55 (dichloromethane: methanol = 8:1)
ESI/MS: m/z 723 [M+H]+ 0 ESI/MS: m/z 723 [M+H] + 0
实施例 5 Example 5
本实施例目的是制备上述通式 6的化合物， 该化合物名为： （4R,7R,8S,9R，10R,13R， 15R, The purpose of this example is to prepare a compound of the above formula 6, which is named: (4R, 7R, 8S, 9R, 10R, 13R, 15R,
16R, 17S)-16-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-己吡喃木糖基]氧基] -7-乙基 -8,9,15-三羟基 -4,8, 10, 13， 15, 17-六甲基 - 1 ,6-二氧- 11 -氮杂 -螺环 [2.14]十七烷 -5-酮。 16R, 17S)-16-[[3,4,6-Trideoxy-3-(dimethylamino)-β-hexylpyranosyl]oxy]-7-ethyl-8,9,15 -Trihydroxy-4,8,10,13,15-hexamethyl-1,6-dioxo-11-aza-spiro[2.14]heptadecan-5-one.
28 28
替换页 （细则第 26条) Replacement page (Article 26)
Figure imgf000030_0001
用甲醇 （300mLx2 ) 替换化合物 5的粘稠液中的残留溶剂， 每次， 最后浓缩液补加甲醇 至 2200mL， 转移至 5000mL三口反应瓶中加入钯碳 95g， 甲酸铵 85g， 置水浴锅中 50°C保温 反应 2小时， 反应毕， 放冷至 30°C以下， 过滤（滤渣加水后密封低温保存） ' 滤液 65°C减压 浓缩至 l lOOmL, 20分钟内缓缓加入到 3300mL水中， 用 10% (w/v) 的氢氧化钠溶液调 pH 至 10.5-11。 室温条件下搅拌析晶 1 小时， 滤过， 滤饼用甲醇-水 （1 : 3 ) 鶴， 40。C常压干 燥 10小时即得 172g脱保护的化合物 6。收率 : 54.4% 。HPLC测定纯度：94.4%。 (应用 WATERS ACQUITY UPLC BEH C18色谱柱 (2.1x50mm, 1.7μιη) ; 流动相为乙腈 -O.Olmo L 乙酸铵 ( 55:45 )；流速 0.20mLAnin，保留时间 2.77min;检测波长 210nm;柱温 40Ό ,进样量 2.5μ1。 ) 13C-NMR(400MHz)6： 176.5(15-0-C=0)； 94.5(C-6-0-l'-
Figure imgf000030_0001
Replace the residual solvent in the viscous liquid of compound 5 with methanol (300mLx2), and add the methanol to 2200mL of the final concentrate. Transfer to a 5000mL three-neck reaction flask, add 95g of palladium on carbon, 85g of ammonium formate, and set in a water bath. The reaction was kept at °C for 2 hours. After the reaction was completed, it was allowed to cool to below 30 °C. Filtration (the filter residue was sealed with water and stored at a low temperature). The filtrate was concentrated to l lOOmL under reduced pressure at 65 ° C, and slowly added to 3300 mL of water within 20 minutes. 10% (w/v) sodium hydroxide solution was adjusted to pH 10.5-11. The mixture was stirred and crystallized at room temperature for 1 hour, filtered, and the filter cake was methanol-water (1:3) crane, 40. C was dried under normal pressure for 10 hours to obtain 172 g of deprotected compound 6. Yield: 54.4%. The purity was determined by HPLC: 94.4%. (Apply WATERS ACQUITY UPLC BEH C 18 column (2.1x50mm, 1.7μιη); mobile phase is acetonitrile-O.Olmo L ammonium acetate (55:45); flow rate 0.20mL Anin, retention time 2.77min; detection wavelength 210nm; column temperature 40Ό, injection volume 2.5μ1.) 1 3 C-NMR (400MHz) 6: 176.5 (15-0-C=0); 94.5 (C-6-0-l'-
C) ;84.2(C-2');76.1;75.4;74.7;72.3;68.4;67.8;62.3;57.3;49.6;43.0;40.3;40.2;40.0;39.8(3*-NMe2),39.5 ;39.2;38.9;38.7;35.2;30.4;28.6;26.2;21.36;20.9;20.3;17.0;16.5;13.2;10.4;7.7 C); 84.2 (C-2');76.1;75.4;74.7;72.3;68.4;67.8;62.3;57.3;49.6;43.0;40.3;40.2;40.0; 39.8 (3*-NMe 2 ), 39.5; 38.9;38.7;35.2;30.4;28.6;26.2;21.36;20.9;20.3;17.0;16.5;13.2;10.4;7.7
^-NMRWOOMHz^: 4.84-4.87(m,2H), 4.38-4.40(d,lH^/=8Hz),  ^-NMRWOOMHz^: 4.84-4.87 (m, 2H), 4.38-4.40 (d, lH^/=8Hz),
3.94(s,lH),3.50-3.63(m,3H), 3.32-3.41(m,2H), 3.18(s,3H), 2.55 (s,6H), 2.26-2.48 (m,4H), 3.94 (s, lH), 3.50-3.63 (m, 3H), 3.32-3.41 (m, 2H), 3.18 (s, 3H), 2.55 (s, 6H), 2.26-2.48 (m, 4H),
1.74-1.98(m,4H), 1.35-1.67(m,6H), 1.03-1.25(m,20H), 0.72-0.96(m,6H). 1.74-1.98 (m, 4H), 1.35-1.67 (m, 6H), 1.03-1.25 (m, 20H), 0.72-0.96 (m, 6H).
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 588 [M+H]十。 以下实施例 6~222的目的均是制备本发明中如通式 I所示的化合物。  ESI/MS: m/z 588 [M+H] ten. The purpose of the following Examples 6 to 222 is to prepare a compound of the present invention as shown in the formula I.
实施例 6 Example 6
(21，38，411,51 ,81，101 ,111 ,128,133,141 -13-[(正丙氨基)甲基]-11-[[3，4,6-三脱氧-3-(二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10，13-四羟基 -3,5,8,10,12，14-六甲基 -1-氧-杂 -6-氮杂环 十五垸 -15-酮磷酸盐 (21,38,411,51,81,101,111,128,133,141 -13-[(n-propylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethylamino) -β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1- Oxy-hetero-6-azacyclopentadecane-15-ketophosphate
Figure imgf000030_0002
Figure imgf000030_0002
在20(^1^三口反应瓶中投入2(^(41，71，88,91 ,101，131， 15R, 16R, 17S)-16-[[3，4,6-三脱氧 -3- (二甲棊氨基) -β-己吡喃木糖基]氧基] -7-乙基 -8,9,15-三羟基 -4,8,10,13，15，17-六甲基 -1,6-二氧 -11-氮杂 -螺环 [2.14]十七垸 -5-酮 （即化合物 6) , 加入异丙醇 lOOmL, 正丙胺 54mL， 52°C保 温反应 29-30h， 反应液 70°C减压浓缩至 45mL， 转入 500mL三口反应瓶中加入 200mL无水 替换页 （细则第 26条) 乙醇和 16mL水， 在 30分钟内 （保证反应液温度为 30°C以下） 滴入 6g磷酸加 90mL无水乙 醇的混合溶液， 滴加完毕保持在 25-30'C范围内反应 18小时， 过滤， 60。C烘干 4小时可得标 题化合物。 In the 20 (^1^ three-mouth reaction flask, put 2 (^(41,71,88,91,101,131, 15R, 16R, 17S)-16-[[3,4,6-trideoxy-3-( Dimethyl hydrazide amino) -β-hexyranopyranosyl]oxy]-7-ethyl-8,9,15-trihydroxy-4,8,10,13,15,17-hexamethyl-1 ,6-Dioxo-11-aza-spiro[2.14]heptadecan-5-one (ie compound 6), adding isopropanol 100 mL, n-propylamine 54 mL, incubation at 52 ° C for 29-30 h, reaction solution Concentrate to 45 mL under reduced pressure at 70 ° C, transfer to a 500 mL three-neck reaction flask and add 200 mL of anhydrous replacement page (Article 26) Ethanol and 16mL of water, within 30 minutes (guaranteed the temperature of the reaction solution is below 30 ° C), a mixture of 6g of phosphoric acid and 90mL of absolute ethanol was added dropwise, and the reaction was kept in the range of 25-30'C for 18 hours after the addition. , 60. The title compound was obtained by drying for 4 hours.
TLC Rf=0.47(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.47 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 048 [M+H]  ESI/MS: m/z 048 [M+H]
实施例 7 Example 7
(21，38,41 ,511，81 ,101，1111，128,138，141 )-13-[(环丙氨基）甲基]-11-[[3，4，6-三脱氧-3-(二甲基氨 基)- β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环 十五垸 -15-酮 （结构式见下）  (21,38,41,511,81,101,1111,128,138,141)-13-[(cyclopropylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethyl) Benzyl)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl -1-Oxo-hetero-6-azetidine, heptadecane-15-one (see below for structural formula)
Figure imgf000031_0001
于 50mL 圆底烧瓶中， 将化合物 6(0.35g，0.4mmoL)， 碘化钾 (2.32g,14mmoL)和环丙胺 (2.43mL，2.00g，35mmoL)在甲醇 (30mL)中 50°C搅拌 2天。浓缩，将剩余物溶于水 (50mL)和乙酸 乙酯 (100mL)。 静置分层后， 含水层用乙酸乙酯 (3x50mL)洗涤。 合并有机相， 用饱和碳酸氢 钠水溶液 (50mL)、 盐水 (40mL)洗涤， 用无水硫酸钠干燥， 过滤， 滤液真空浓缩得粗品。 硅胶 色谱纯化， 用甲醇 ： 二氯甲垸 ： 氨水 (4~6： 93.5-95.6： 0.4)洗脱； 得到 0.38g标题化合物。
Figure imgf000031_0001
Compound 6 (0.35 g, 0.4 mmoL), potassium iodide (2.32 g, 14 mmoL) and cyclopropylamine (2.43 mL, 2.00 g, 35 mmol) were stirred in methanol (30 mL) at 50 ° C for 2 days in a 50 mL round bottom flask. Concentrate and dissolve the residue in water (50 mL)EtOAcEtOAc After standing to separate the layers, the aqueous layer was washed with ethyl acetate (3×50 mL). The combined organic layers were washed with EtOAc EtOAc. Purify by silica gel chromatography eluting with EtOAc:EtOAc:EtOAc:
TLC ¾=0.47(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.47 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 646 [M+H]  ESI/MS: m/z 646 [M+H]
实施例 8 Example 8
(211,33,411,511，811,10 ，111，128,138，141 )-13-[(正丁氨基）甲基]-11-[[3，4,6-三脱氧-3-(二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环 十五烷 -15-酮 （结构式见下）  (211, 33, 411, 511, 811, 10, 111, 128, 138, 141)-13-[(n-butylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethylamino)- β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo -hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000031_0002
Figure imgf000031_0002
将化合物 6 (0.176g, 0.2mmoL)， 四丁基碘化铵 (0.74，2.0mmoL)和正丁胺 (0.395mL， 0.2938, 4mmoL)在甲醇 (5mL)中的溶液在 50Ό搅拌 2天。浓缩，将剩余物溶于水 (20 mL)和乙酸乙酯（20 mL；)。 静置分层后， 含水层用乙酸乙酯 (3x20 mL)洗涤。 合并有机萃取物用盐水 (40 mL)洗涤， 用无水硫酸钠干燥， 过滤， 滤液真空浓缩， 得粗品。硅胶色谱纯化， 用甲醇 ： 二氯甲烷 ： 氨 水 (4~6： 93.5-95.6： 0.4)洗脱， 得 0.0888g标题化合物。  A solution of compound 6 (0.176 g, 0.2 mmoL), tetrabutylammonium iodide (0.74, 2.0 mmol) and n-butylamine (0.395 mL, 0.2938, 4 mmol) in methanol (5 mL) was stirred at 50 Torr for 2 days. Concentrate and dissolve the residue in water (20 mL) and ethyl acetate (20 mL; After standing to separate layers, the aqueous layer was washed with ethyl acetate (3×20 mL). The combined organic extracts were washed with EtOAc EtOAc m. Chromatography on silica gel eluting with EtOAc: EtOAc (EtOAc)
TLC R产 0.47(二氯甲垸： 甲醇 =5:1)  TLC R yield 0.47 (dichloroformamidine: methanol = 5:1)
30 30
替换页 （细则第 26条) ESI/MS: m/z662 [M+H] Replacement page (Article 26) ESI/MS: m/z662 [M+H]
实施例 9 Example 9
(2! 334 51 ,811101,111,1281381411)-11-[[34,6-三脱氧 -3- (二甲基氨基）甲基 -β-D-己吡喃木 糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-((2- 基-3-甲基-苄胺基)甲基) -35810,12,14-六甲基 -1-氧-杂 -6-氮杂环十五院 -15-酮 （结  (2! 334 51 , 811101, 111, 1281381411) -11-[[34,6-Trideoxy-3-(dimethylamino)methyl-β-D-hexylpyranosyl]oxy] - 2-ethyl-3,4,10,13-tetrahydroxy-13-((2-yl-3-methyl-benzylamino)methyl)-35810,12,14-hexamethyl-1-oxo -hetero-6-nitrogen heterocyclic fifteenth hospital-15-ketone (knot
Figure imgf000032_0001
Figure imgf000032_0001
将 500mg化合物 6在 lOOmL圆底烧瓶中溶于 2mL2-羟基 -3-甲基-苄胺和 5mL异丙醇中。 加入催化量 (20mg)的吡啶鎗盐酸盐并将溶液在 50°C加热 2天。 加入 50mL饱和 NaHC03终止 反应， 用 3x50mLCH2Cl2萃取， 并用 Na2S04干燥。 过滤， 浓缩滤液， 得到粗产物。用硅胶柱 色谱进一步纯化，用甲醇 ： 二氯甲垸 ：氨水 (4~6： 93.5-95.6： 0.4)洗脱，得标题化合物 0.24g TLC Rf=0.42(二氯甲烷： 甲醇 =5:1) 500 mg of compound 6 was dissolved in 2 mL of 2-hydroxy-3-methyl-benzylamine and 5 mL of isopropanol in a 100 mL round bottom flask. A catalytic amount (20 mg) of pyridine gun hydrochloride was added and the solution was heated at 50 °C for 2 days. Add 50mL reaction was quenched with saturated NaHC0 3, extracted with 3x50mLCH 2 Cl, and dried over Na 2 S0 4. Filtration and concentration of the filtrate gave a crude material. Purification by silica gel column chromatography, eluting eluting elut elut elut elut elut eluting elut
ESI/MS: m/z 726 [M+H]  ESI/MS: m/z 726 [M+H]
实施例 10 Example 10
(21,38411,511,81 ,101 ,111 125138,141)-11-[[3,46-三脱氧-3-(二甲基氨基)-&-0-己吡喃木糖基] 氧基] -2-乙基 -3,410,13-四羟基 -35810,1214-六甲基 -13-((345-三甲氧基-苄基胺)甲基 -1-氧- 杂 -6-氮杂环十五垸 -15-酮 （结构式  (21,38411,511,81,101,111 125138,141)-11-[[3,46-Trideoxy-3-(dimethylamino)-&-0-hexylpyranosyl]oxy ]-2-Ethyl-3,410,13-tetrahydroxy-35810,1214-hexamethyl-13-((345-trimethoxy-benzylamine)methyl-1-oxo-hetero-6-azacyclocycle Fifteen -15-ketone (structural formula
Figure imgf000032_0002
Figure imgf000032_0002
将实施例 8 中的 "正丁胺 (0.395mL, 0.2938, 4mmoL)"改为使用 "3,4,5-三甲氧基 -苄胺 (0.395mL)" ， 其余同实施例 8。 得 0.08g标题化合物。  The "n-butylamine (0.395 mL, 0.2938, 4 mmoL)" in Example 8 was changed to use "3,4,5-trimethoxy-benzylamine (0.395 mL)", and the rest was the same as in Example 8. 0.08 g of the title compound was obtained.
Rf=0.42(二氯甲垸： 甲醇 =5:1)  Rf = 0.42 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 786[M+H]+ ESI/MS: m/z 786[M+H] +
实施例 11 Example 11
(2! ,384!^51 81 101 111 128,138,141)-13-[(2-甲氧基乙氨基）甲基] -11-[[3,4,6-三脱氧 -3- (二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -341013-四羟基 -35810,1214-六甲基小氧-杂 -6-氮 杂环十五垸 -15-酮 （结构式见下）  (2!,384!^51 81 101 111 128,138,141)-13-[(2-methoxyethylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethylamino) -β-D-hexylpyranosyl]oxy]-2-ethyl-341013-tetrahydroxy-35810,1214-hexamethyloxy-hetero-6-azacyclopentades-15- Ketone (see below for structural formula)
31 31
替换页 （细则第 26条)
Figure imgf000033_0001
Replacement page (Article 26)
Figure imgf000033_0001
将化合物 6 (0.35g,0.4mmoL), 碘化钾 (2.32g,14mmoL)和 1-甲氧基乙胺 (2.43mL)在异丙醇 (30mL)中的溶液在 50°C搅拌 2天。 浓缩， 将剩余物溶于水 (50mL)和乙酸乙酯（lOOmL) 。 静 置分层后， 含水层用乙酸乙酯（3x50mL)洗涤。合并有机相， 用饱和碳酸氢钠水溶液 (50 mL)、 盐水 (40 mL)洗涤， 用 Na2S04干燥， 过滤， 滤液真空浓缩， 得粗品。 硅胶色谱纯化， 用甲醇 ： 二氯甲垸：氨水 (4~6： 93.5-95.6： 0.4)洗脱， 得到 0.38g标题化合物。 A solution of compound 6 (0.35 g, 0.4 mmol), potassium iodide (2.32 g, 14 mmol) and 1-methoxyethylamine (2.43 mL) in isopropyl alcohol (30 mL) was stirred at 50 ° C for 2 days. Concentrate and dissolve the residue in water (50 mL) and ethyl acetate (lOOmL). After standing to separate the layers, the aqueous layer was washed with ethyl acetate (3×50 mL). The combined organic phases were washed with saturated aqueous sodium bicarbonate (50 mL), brine (40 mL) was washed, dried with Na 2 S0 4, filtered and the filtrate concentrated in vacuo to give the crude product. Chromatography on silica gel eluting with EtOAc:EtOAc (EtOAc:EtOAc)
TLC ¾=0.43(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.43 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 664 [M+H]+ ESI/MS: m/z 664 [M+H] +
实卿 J Shi Qing J
(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(哌啶基）甲基 ]-11-[[3，4，6-三脱氧 -3-(二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环 十五烷 -15-酮 （结构式见下） (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(piperidinyl)methyl]-11-[[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000033_0002
Figure imgf000033_0002
在 200mL三口反应瓶中投入 0.5g化合物 6， 加入异丙醇 lOOmL, 哌啶 5mL， 50'C保温 反应 36h， 反应液 70'C减压浓缩至 45mL， 转入 250mL三口反应瓶中加入 lOOmL无水乙醇和 5mL水， 在 30分钟内 （保证反应液温度为 30Ό以下）滴入 2g磷酸加 90mL无水乙醇的混合 溶液， 滴加完毕保持在 25-3CTC范围内反应 18小时， 过滤， 60°C烘干 4小时可得 0.32g标题 化合物。  0.5 g of compound 6 was placed in a 200 mL three-neck reaction flask, 100 mL of isopropanol and 5 mL of piperidine were added, and the reaction was kept at 50 ° C for 36 h. The reaction solution was concentrated to 45 mL under reduced pressure at 70 ° C, and transferred to a 250 mL three-neck reaction flask to add 100 mL. Water ethanol and 5mL water, within 30 minutes (guaranteed the temperature of the reaction solution is less than 30 )), a mixture of 2g of phosphoric acid and 90mL of absolute ethanol was added dropwise, and the reaction was kept in the range of 25-3CTC for 18 hours, filtered, 60°. Drying for 4 hours gave 0.32 g of the title compound.
TLC ¾=0.47(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.47 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 674 [M+H]十。  ESI/MS: m/z 674 [M+H] ten.
实施例 13 Example 13
(2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(吗啉基）甲基] -11 -[[3,4,6-三脱氧 -3-(二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环 十五烷 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(morpholinyl)methyl]-11-[[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000033_0003
Figure imgf000033_0003
32  32
替换页 （细则第 26条) 200mL三口反应瓶中投入 0.5g化合物 6, 加入异丙醇 lOOmL, 吗啉 4.5mL， 50。C保温反 应 36h， 反应液 70°C减压浓缩， 加 lOOmL纯化水搅拌 10分钟， 用 3x50mL二氯甲垸萃取。 合并有机相， 用无水硫酸钠干燥、 过滤， 滤液减压浓缩蒸干得 0.34g标题化合物粗品。 通过 硅胶柱色谱进一步纯化，用甲醇 ： 二氯甲烷 ： 氨水 (4~6 : 93.5~95.6 : 0.4)洗脱，得标题化合物。 Replacement page (Article 26) 0.5 g of Compound 6 was placed in a 200 mL three-neck reaction flask, and 100 mL of isopropanol and 4.5 mL of morpholine were added. The reaction was incubated for 36 hours, and the reaction mixture was concentrated under reduced pressure at 70 ° C., and then, 100 mL of purified water was stirred for 10 minutes, and extracted with 3 x 50 mL of dichloromethane. The organic layer was combined, dried over anhydrous sodium sulfate Further purification by silica gel column chromatography eluting with EtOAc EtOAc EtOAc
TLC Ri=0.47(二氯甲垸： 甲醇 =5:1)  TLC Ri=0.47 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 676 [M+H]十。  ESI/MS: m/z 676 [M+H] ten.
实施例 14 Example 14
(2R，3S，4R，5R,8R,10R,11R，12S,13S,14R)-13- [(叔丁氨基）甲基] -11-[[3,4，6-三脱氧 -3- (二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12，14-六甲基小氧-杂 -6-氮杂环 十五烷 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(tert-Butylamino)methyl]-11-[[3,4,6-trideoxy-3- ( Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-six Methyl small oxygen-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000034_0001
Figure imgf000034_0001
在 200mL三口反应瓶中投入 lg化合物 6， 加入异丙醇 lOOmL, 叔丁胺 4.5mL， 50°C保 温反应 36h, 反应液 70°C减压浓缩， 加 lOOmL纯化水搅拌 10分钟， 用 3><50mL二氯甲烷萃 取。 合并有机相， 用无水硫酸钠干燥， 过滤， 滤液减压浓缩蒸干可得 0.4g粗品。 用硅胶柱色 谱进一步纯化， 用甲醇 ： 二氯甲烷 ：氨水 (4~6 ： 93.5~95.6： 0.4)洗脱， 得到标题化合物。  In a 200 mL three-neck reaction flask, lg compound 6 was charged, 100 mL of isopropanol and 4.5 mL of t-butylamine were added, and the reaction was kept at 50 ° C for 36 h. The reaction solution was concentrated under reduced pressure at 70 ° C, and 100 mL of purified water was added and stirred for 10 minutes, using 3><50 mL. Extracted with dichloromethane. The organic phase was combined, dried over anhydrous sodium sulfate, filtered, and evaporated. Further purification by column chromatography on silica gel eluting elut elut elut elut elut elut elut
TLC Rf=0.47(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.47 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 662 [M+H]+ 0 ESI/MS: m/z 662 [M+H] + 0
实施例 15 Example 15
(2ΙΙ,38,4¾5ίΙ，8ΙΙ,10Ι ,11Ι ，128，138，14Ι )-13- [(苄基氨基)甲基] -11-[[3，4，6-三脱氧 -3- (二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮杂环 十五垸 -15-酮 （结构式见下）  (2,3,4,6-trideoxy-3-(dimethyl) -amino-)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl Small oxygen-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000034_0002
Figure imgf000034_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "苄胺 5mL" 其余同实施例 14。 中间获 得 0.28g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "benzylamine 5 mL", and the rest was the same as in Example 14. A crude product of 0.28 g was obtained in the middle to give the title compound.
TLC Rf=0.55(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.55 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 696 [M+H]十。  ESI/MS: m/z 696 [M+H] ten.
16  16
(21 ,38,41 551 ，811,101 511« 28,138，14 -13-[(环戊氨基)甲基]-11-[[3，4,6-三脱氧-3-(二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10,12,14-六甲基小氧-杂 -6-氮杂环 替换页 （细则第 26条) 十五烷 -15-酮 （结构式见下) (21,38,41 5 51 ,811,101 5 11« 28,138,14 -13-[(cyclopentylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethylamino)) -β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy- Hetero-6-nitrogen heterocycle replacement page (Article 26) Pentadecane-15-one (see below for structural formula)
Figure imgf000035_0001
Figure imgf000035_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "四氢吡咯 5mL" , 其余同实施例 14。 中 间获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "tetrahydropyrrole 5 mL", and the rest was the same as in Example 14. Intermediate was obtained in 0.25 g of crude product to give the title compound.
TLC ¾=0.55(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4 = 0.55 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 660 [M+H]  ESI/MS: m/z 660 [M+H]
实施例 17 Example 17
(2R,3S4R5R8R,10R11R12S13S14R)-13- [(苯氨基）甲基] -11-[[3,4,6-三脱氧 -3- (二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8101214-六甲基小氧-杂 -6-氮杂环 十五垸 -15-酮 （结构式见下）  (2R,3S4R5R8R,10R11R12S13S14R)-13-[(phenylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-hexyryl xylose Ethyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8101214-hexamethyloxy-hetero-6-azetidine-decadepin-15-one (structural formula) See below)
Figure imgf000035_0002
Figure imgf000035_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "苯胺 5mL"， 其余同实施例 14。 中间获 得 0.30g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "aniline 5 mL", and the rest was the same as in Example 14. A crude product of 0.30 g was obtained in the middle to give the title compound.
TLC Rf=0.55(二氯甲烷： 甲醇 =7:1)  TLC Rf = 0.55 (dichloromethane: methanol = 7:1)
ESI/MS: m/z682 [M+H]+ ESI/MS: m/z682 [M+H] +
实施例 1 Example 1
(21138,41,51^81 101 111 128,138,141)-13-[(1-甲氧基丙氨基)甲基]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,1012,14-六甲基 -1-氧 -杂 -6-氮杂环十五垸 -15-酮 （结构式见下）  (21138,41,51^81 101 111 128,138,141)-13-[(1-methoxypropylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethylamino) -β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,1012,14-hexamethyl-1-oxo- Hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000035_0003
Figure imgf000035_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "1-甲氧基丙胺 5mL"， 其余同实施例 14 中间获得 0.30g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "1-methoxypropylamine 5 mL", and the residue obtained in the same manner as in Example 14 was obtained.
TLC Rf=0.55(二氯甲烷： 甲醇 =7:1)  TLC Rf = 0.55 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 682 [M+H]  ESI/MS: m/z 682 [M+H]
实施例 19 Example 19
34  34
替换页 （细则第 26条) (2 ,3S,4 ,5R,8R,10R,11R12S13S14R)-13- [(正己氨基）甲基] -11-[[3,4,6-三脱氧 -3- (二甲 基氨基) -P-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟 -3,5810,1214-六甲基 -1-氧-杂 -6-氮杂 环十五焼 -15-酮 （结构式见下） Replacement page (Article 26) (2,3S,4,5R,8R,10R,11R12S13S14R)-13-[(n-hexylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethylamino)-PD -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5810,1214-hexamethyl-1-oxo-hetero-6-azetidine Wuqi-15-ketone (see below for structural formula)
Figure imgf000036_0001
Figure imgf000036_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "正己胺 5mL" , 其余同实施例 14。 中间 获得 0.33g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "n-hexylamine 5 mL", and the rest was the same as in Example 14. 0.33 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.51(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.51 (dichloromethane: methanol = 7:1)
ESI/MS: m/z690[M+H]  ESI/MS: m/z 690 [M+H]
实施例 20 Example 20
(2R,3S,4R,5R,8R,10R,llR,12S,13S14R)-13-[(2-乙氧基丙氨基)甲基] -11-[[3,46-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3410,13-四羟基 -3581012,14-六甲基小氧 -杂 -6-氮杂环十五垸 -15-酮 （结构式见  (2R,3S,4R,5R,8R,10R,llR,12S,13S14R)-13-[(2-ethoxypropylamino)methyl]-11-[[3,46-tripleoxy-3-( Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3410,13-tetrahydroxy-3581012,14-hexamethyloxy-hetero-6-azacyclocycle Fifteen 垸-15-ketone (see structure)
Figure imgf000036_0002
Figure imgf000036_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-乙氧基丙胺 5mL" ， 其余同实施例 14 中间获得 0.33g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-ethoxypropanamine 5 mL", and the residue was obtained in the same manner as in Example 14 to give the title compound.
TLC RiN).51(二氯甲垸： 甲醇 =7:1)  TLC RiN).51 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z692 [M+H]  ESI/MS: m/z692 [M+H]
实施例 21 Example 21
(2!^33,4¾51 81,101,111 123133,1411)-13-[(二乙氨基)甲基]-11-[ (4-二甲基氨基 -3-羟基 -6-甲基 -β-D-己吡喃木糖基]氧基] -2-乙基 -3,410, 13-四羟基 -3,5,810,12,14-六甲基 -1 -氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下）  (2!^33,43⁄451 81,101,111 123133,1411)-13-[(diethylamino)methyl]-11-[ (4-dimethylamino-3-hydroxy-6-methyl-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-3,410,13-tetrahydroxy-3,5,810,12,14-hexamethyl-1 -oxo-hetero-6-azacyclopentadecane-15 -ketone (see below for structural formula)
Figure imgf000036_0003
Figure imgf000036_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "二乙胺 5mL"， 其余同实施例 14。 中间 获得 0.24g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "diethylamine 5 mL", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.51(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.51 (dichloromethane: methanol = 7:1)
ESI/MS: m/z662 [M+H]+ 替换页 （细则第 26条) 实施例 22 ESI/MS: m/z662 [M+H] + replacement page (Article 26) Example 22
(2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[( N-甲基丁氨基）甲基] -11-[[3，4，6-三脱氧 -3_(二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5，8,10，12,14-六甲基小氧 -杂 -6-氮杂环十五烷 -15-酮 （结构式见 (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(N-methylbutylamino)methyl]-11-[[3,4,6-trideoxy - 3 _(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 ,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000037_0001
Figure imgf000037_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "N-甲基正丁胺 5mL"， 其余同实施例 14。 中间获得 0.23g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "N-methyl-n-butylamine 5 mL", and the rest was the same as in Example 14. 0.23 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.51 (二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.51 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 676 [M+H]+ ESI/MS: m/z 676 [M+H] +
实施例 23 Example 23
(21，38,411,51，81 ,101 ,111，128，138，141 )-13-[( ^甲基丙氨基)甲基]-1 [ (4-二甲基氨基 -3-羟基 -6-甲基 -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5,8,10，12，14-六甲基 -1-氧-杂 -6-氮 杂环十五烧 -15-酮 （结构式见下）  (21,38,411,51,81,101,111,128,138,141 )-13-[( ^Methylpropylamino)methyl]-1 [(4-dimethylamino-3-hydroxy-6- Methyl-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl- 1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000037_0002
Figure imgf000037_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "N-甲基-正丙胺 5mL"， 其余同实施例 14。 中间获得 0.2g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "N-methyl-n-propylamine 5 mL", and the rest was the same as in Example 14. 0.2 g of crude product was obtained in the middle to give the title compound.
TLC RfK).51(二氯甲垸： 甲醇 =7:1)  TLC RfK).51 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 662 [M+H]+ ESI/MS: m/z 662 [M+H] +
实施例 24 Example 24
(21 ,38，411,51，81 ,101，111，128,135,141 )-13-[(乙基氨基)甲基]-11-[[3,4，6-三脱氧-3-(二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12，14-六甲基小氧-杂 -6-氮杂环 十五垸 -15-酮 （结构式见下） (21,38,411,51,81,101,111,128,135,141 )-13-[(ethylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethylamino) -β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy -hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000037_0003
Figure imgf000037_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "乙胺 5mL" ， 其余同实施例 14。 中间获 得 0.2g粗品， 最终得标题化合物。 替换页 （细则第 26条) TLC RfN).51(二氯甲垸： 甲醇 =7:1) The "t-butylamine 4.5 mL" in Example 14 was changed to use "ethylamine 5 mL", and the rest was the same as in Example 14. 0.2 g of crude product was obtained in the middle to give the title compound. Replacement page (Article 26) TLC RfN).51 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 634 [M+H]+ ESI/MS: m/z 634 [M+H] +
实施例 25 Example 25
(2¾38，41 ,51，811，101，111，128,138,1411)-13-[(^甲基乙氨基)甲基]-11-[ (4-二甲基氨基 -3-羟基 -6-甲基 -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12，14-六甲基 -1-氧-杂 -6-氮 杂环十五垸 -15-酮 （结构式见下）  (23⁄438,41,51,811,101,111,128,138,1411)-13-[(^methylethylamino)methyl]-11-[(4-dimethylamino-3-hydroxy-6-A --β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1 -Oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000038_0001
Figure imgf000038_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "N-甲基乙胺 5mL" ， 其余同实施例 14。 中间获得 0.29g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "N-methylethylamine 5 mL", and the rest was the same as in Example 14. 0.29 g of crude product was obtained in the middle to give the title compound.
Rf=0.48(二氯甲垸： 甲醇 =7:1)  Rf = 0.48 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 648 [M+H]  ESI/MS: m/z 648 [M+H]
实施例 26 Example 26
(21，38,411,51，811，101 ,11 ，123，138,141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基)-&-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12，14-六甲基 -13-[(2-三氟乙氨基)甲基] -1-氧-杂 -6-氮杂 环十五烷 -15-酮 （结构式见下）  (21,38,411,51,811,101,11,123,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-&-0-hexyranidose ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(2-trifluoroethylamino)methyl ]-1-Oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000038_0002
Figure imgf000038_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-三氟乙胺 5mL"， 其余同实施例 14。 中 间获得 0.28g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-trifluoroethylamine 5 mL", and the rest was the same as in Example 14. In the middle, 0.28 g of crude product was obtained, which gave the title compound.
TLC RfN).51(二氯甲烷： 甲醇 =7:1)  TLC RfN).51 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 688 [M+H]  ESI/MS: m/z 688 [M+H]
实施例 27 Example 27
(2R,3S，4R，5R，8R，10R，llR,12S，13S，14R)-U-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12,14-六甲基 -13-((3-硝基苄基氨基)甲基 )小氧-杂 -6-氮 杂环十五垸 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,llR,12S,13S,14R)-U-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexidyl Cycloxylosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-((3-nitrobenzyl) Base amino)methyl)methanol-hetero-6-azetidine-pentadecane-15-one (see below for structural formula)
Figure imgf000038_0003
Figure imgf000038_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "间硝基苄胺 5mL" , 其余同实施例 14。 中间获得 0.25g粗品， 最终得标题化合物。 替换页 （细则第 26条) TLC R ).49(二氯甲烷： 甲醇 =7:1) The "t-butylamine 4.5 mL" in Example 14 was changed to use "m-nitrobenzylamine 5 mL", and the rest was the same as in Example 14. 0.25 g of crude product was obtained in the middle to give the title compound. Replacement page (Article 26) TLC R ).49 (dichloromethane: methanol = 7:1)
ESI/MS: lz 741 [M+H]+ ESI/MS: lz 741 [M+H] +
实施例 28 Example 28
(211,38，411,511,811,101，111，128,138，141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基) -0-己吡喃木 糖基]氧基] -2-乙基 _3，4，10,13-四羟基 -13-[(1-羟基 -乙基氨基) -甲基 ]-3,5，8,10，12，14-六甲基小氧- 杂 -6-氮杂环十五垸 -15-酮 （结构式见下 (211, 38, 411, 511, 811, 101, 111, 128, 138, 141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexylopyranosyl]oxy] -2 - ethyl _ 3, 4, 10,13- tetrahydroxy-13 - [(1-hydroxy - ethylamino) - methyl] -3,5,8,10,12,14- small hexamethyl oxo - Hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000039_0001
Figure imgf000039_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 " 1-羟基乙胺 5mL"， 其余同实施例 14。 中 间获得 0.27g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "1-hydroxyethylamine 5 mL", and the rest was the same as in Example 14. In the middle, 0.27 g of crude product was obtained, which gave the title compound.
Rf=0.49(二氯甲垸： 甲醇 =7:1)  Rf = 0.49 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 650 [M+H]† ESI/MS: m/z 650 [M+H] †
实施例 29 Example 29
(21 ,38，411，51，81，101 ,111 ,128,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)甲基-3-0-己吡喃木 糖基]氧基] -13- [(二甲基氨基)甲基] -2-乙基 -3，4，10,13-四羟基 -3,5,8，10，12，14-六甲基小氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  (21,38,411,51,81,101,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)methyl-3-0-hexidyl Iso-xylyloxy]-13-[(dimethylamino)methyl]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000039_0002
Figure imgf000039_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "二甲胺 5mL"， 其余同实施例 14。 中间 获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "dimethylamine 5 mL", and the rest was the same as in Example 14. 0.25 g of crude product was obtained in the middle to give the title compound.
TLC R^0.49(二氯甲烷： 甲醇 =7:1)  TLC R^0.49 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 634 [M+H]  ESI/MS: m/z 634 [M+H]
实施例 30 Example 30
(21 ,38,41，5] ,81 ,101 ,111，128，138，141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2- 基 -3,4,10,13-四羟基 -13- [(咪唑基)甲基] -3，5，8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五 垸 -15-酮（结构式见下）  (21,38,41,5] ,81 ,101 ,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl Pyranosyl]oxy]-2-yl-3,4,10,13-tetrahydroxy-13-[(imidazolyl)methyl] -3,5,8,10,12,14-hexa Keith-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000039_0003
Figure imgf000039_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "咪唑 4g" , 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "imidazole 4g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.49(二氯甲垸： 甲醇 =7:1) 替换页 （细则第 26条) ESI/MS: m/z 657 [M+H]+ TLC Rf = 0.49 (dichloromethane: methanol = 7:1) Replacement page (Article 26) ESI/MS: m/z 657 [M+H] +
实施例 31 Example 31
(2R,3S，4R，5R，8R,10R,11R,12S,13S，14R)-13- [(双 (2-羟乙基）氨）甲基] -l l-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8,10，12,14-六甲基小氧 -杂 -6-氮杂环十五垸 -15-酮 （结构式见下 (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13- [(bis(2-hydroxyethyl)amino)methyl]-l l-[[3,4,6 - trideoxy - 3 - (dimethylamino) -β-D- xylopyranosyl hexyl] oxy] -2-ethyl -3,4,10,13- tetrahydroxy -3,5,8, 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000040_0001
Figure imgf000040_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "双 (2-羟基乙基)胺 4g"， 其余同实施例 14。 中间获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "bis(2-hydroxyethyl)amine 4g", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
TLC RfM).49(二氯甲垸： 甲醇 =7:1)  TLC RfM).49 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 694 [M+H]  ESI/MS: m/z 694 [M+H]
实施例 32 Example 32
(21，33，41 ,511,81 ,10] ,1111，128,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木 糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -13- [(吡咯)甲基] -1-氧-杂 -6-氮杂环 十五垸 -15-酮 （结构式见下）  (21,33,41,511,81,10] ,1111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexanpyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(pyrrole)methyl] - 1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000040_0002
Figure imgf000040_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "吡咯 4mL" ， 其余同实施例 14。 中间获 得 0.25g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "pyrrole 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
TLC Rf=0.49(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.49 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 656 [M+H]+ ESI/MS: m/z 656 [M+H] +
实施例 33 Example 33
(2R，3S,4R，5R，8R,10R，l lR,12S，13S,14R)-l l-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3，4，10，13-四羟基 -13-{[(1-轻基-乙基) -甲基氨] -甲基 }-3，5，8，10，12，14-六甲基 -1-氧- 杂 -6-氮杂环十五垸 -15-酮 （结构式见下  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-{[(1-light-ethyl)-methylamino]-methyl}- 3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000040_0003
Figure imgf000040_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "N-甲基 -1-羟基乙胺 4mL"， 其余同实施 例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "N-methyl-1-hydroxyethylamine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.49(二氯甲烷： 甲醇 =7:1)  TLC 3⁄4 = 0.49 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 664 [M+H] 替换页 （细则第 26条) 实施例 34 ESI/MS: m/z 664 [M+H] replacement page (Article 26) Example 34
(2R,3S,4R，5R，8R，10R，l lR,12S，13S,14R)-U-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木 糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12,14-六甲基 -13-{ [1,2,3]三氮唑基 -1-甲基 }-1-氧- 杂 -6-氮杂环十五烷 -15-酮 （结构式见  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-U-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{ [1,2, 3] triazolyl-1-methyl}-1-oxo-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000041_0001
Figure imgf000041_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 " 1，2，3-三氮唑 4g" , 其余同实施例 14。 中 间获得 0.28g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "1,2,3-triazole 4g", and the rest was the same as in Example 14. In the middle, 0.28 g of crude product was obtained, which gave the title compound.
TLC Rf=0.49(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.49 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 658 [M+H]+ ESI/MS: m/z 658 [M+H] +
实施例 35 Example 35
(211,35,411，511,81，101 ,1111，128,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基 3-0-己吡喃木糖基] 氧基] -2-乙基 -3,4，10，13-四羟基 -3，5，8,10，12,14-六甲基 -13- [(炔丙基)氨基甲基 ]小氧-杂 -6-氮杂环 十五垸 -15-酮 （结构式见下）  (211, 35, 411, 511, 81, 101, 1111, 128, 138, 141)-11-[[3,4,6-Trideoxy-3-(dimethylamino 3-0-hexylopyranosyl) Oxygen 2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(propargyl)aminomethyl]oxygen- Hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000041_0002
Figure imgf000041_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-炔丙胺 4mL"， 其余同实施例 14。 中间 获得 0.27g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-propargylamine 4 mL", and the rest was the same as in Example 14. 0.27 g of crude product was obtained in the middle to give the title compound.
TLC Rj=0.55(二氯甲垸： 甲醇 =7:1)  TLC Rj = 0.55 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 644[M+H]+ ESI/MS: m/z 644[M+H] +
实施例 36 Example 36
(21 ,33，41，51，81 ,101 ,111，128,133,1411)-11-[[3,4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8，10，12，14-六甲基 -13-(2-甲基 -咪唑 -1-基-甲基) -1-氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下） (21,33,41,51,81,101,111,128,133,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(2-methyl-imidazole-1 -yl-methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000041_0003
Figure imgf000041_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-甲基咪唑 4g"， 其余同实施例 14。 中 间获得 0.29g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-methylimidazole 4g", and the rest was the same as in Example 14. In the middle, 0.29 g of crude product was obtained, which gave the title compound.
TLC Rf=0.55(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.55 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 671 [M+H]+ ESI/MS: m/z 671 [M+H] +
实施例 37 替换页 （细则第 26条) (2! ,38，4¾511,81 ,101，11 ，128，138，141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基) 0-己吡喃木糖基] 氧基] -13- (二乙烯基氨基甲基） -2-乙基 -3,4,10,13-四羟基 -3,5,8，10,12，14-六甲基小氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下） Example 37 Replacement Page (Rule 26) (2!,38,43⁄4511,81,101,11,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino) 0-hexyranose ]oxy] -13-(divinylaminomethyl)-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy- Hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000042_0001
Figure imgf000042_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "二乙烯胺 4mL" ， 其余同实施例 14。 中 间获得 0.28g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "divinylamine 4 mL", and the rest was the same as in Example 14. In the middle, 0.28 g of crude product was obtained, which gave the title compound.
TLC Rf=0.55(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.55 (dichloromethane: methanol = 7:1)
ESI/MS: mJz 658[M+H]+ ESI/MS: mJz 658[M+H] +
实施例 38 Example 38
(21，38，41，51 ,81，1(¾，11 128，133，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基) -0-己吡喃木 糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -13-[(2-羟基小羟基甲基 -乙基氨基) -甲基 ]-3,5，8,10,12,14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮 （  (21,38,41,51,81,1(3⁄4,11 128,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(2-hydroxy small hydroxymethyl-ethylamino)-methyl]-3,5,8 ,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (
Figure imgf000042_0002
Figure imgf000042_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "二乙醇胺 4mL"， 其余同实施例 14。 中 间获得 0,23g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "diethanolamine 4 mL", and the rest was the same as in Example 14. In the middle, 0,23 g of crude product was obtained, and the title compound was finally obtained.
TLC Rf=0.55(二氯甲烷： 甲醇 =7: 1)  TLC Rf = 0.55 (dichloromethane: methanol = 7: 1)
ESI/MS: m/z 680[M+H]  ESI/MS: m/z 680[M+H]
实施例 39 Example 39
(2 ，38，411,511,811,101，111 ,128,138，1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基) -0-己吡喃木糖基] 氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12，14-六甲基 -13- [(甲氨基)甲基] -1-氧-杂 -6-氮杂环十五 垸 -15-酮 （结构式见下）  (2,38,411,511,811,101,111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexylpyranosyl]oxy]-2 -ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(methylamino)methyl]-1-oxo-hetero-6- Nitroheterocyclopentadecano-15-one (see below for structural formula)
Figure imgf000042_0003
Figure imgf000042_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "甲胺 4mL" ， 其余同实施例 14。 中间获 得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "methylamine 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
TLC Rf=0.55(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.55 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 620[M+H]  ESI/MS: m/z 620[M+H]
实施例 4Q Example 4Q
(2R,3S，4R,5R，8R，10R，l lR，12S，13S,14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 替换页 （细则第 26条) 氧基] -2_乙基 -3，4，10，13-四羟基 -13- (异丙基氨基 -甲基 )-3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环 十五烷 -15-酮 （结构式见下） (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D- Hexylpyranosyl] replacement page (Article 26) Oxy] - 2 _ ethyl - 3,4, 10,13- tetrahydroxy -13- (isopropylamino-methyl) - hexamethyl small -3,5,8,10,12,14- oxo - Hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000043_0001
Figure imgf000043_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "异丙胺 4mL"， 其余同实施例 14。 中间 获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "isopropylamine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC Rf0.51(二氯甲垸： 甲醇 =7:1)  TLC Rf0.51 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 648[M+H〗+ ESI/MS: m/z 648[M+H〗 +
实施例 41 Example 41
(21，38,41，511，81 ,101 ,1111?128，138，141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基) 0-己吡喃木糖基] 氧基] -2-乙基 -3，4，10，13-四羟基 -13- (异丙氨基-甲基) -3，5，8，10，12,14-六甲基 -13-[(3-甲基-丁基氨 基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮 (21,38,41,511,81,101,1111 ? 128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino) 0-hexylpyranose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(isopropylamino-methyl)-3,5,8,10,12,14-hexamethyl-13 -[(3-methyl-butylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one
Figure imgf000043_0002
Figure imgf000043_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3-甲基丁胺 4mL"， 其余同实施例 14。 中 间获得 0.24g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-methylbutylamine 4 mL", and the rest was the same as in Example 14. In the middle, 0.24 g of crude product was obtained, which gave the title compound.
¾=0.53(二氯甲烷： 甲醇 =7:1)  3⁄4=0.53 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 676[M+H]  ESI/MS: m/z 676[M+H]
讓 42  Let 42
(21 ,38,411，511,81 ,101 ,111，128，138，141 )-13-[(>^杂环丙烷基)甲基]-11-[[3,4,6-三脱氧-3-(二甲基 氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4， 10, 13-四羟基 -3,5，8, 10， 12, 14-六甲基小氧-杂 -6-氮杂 环十五院 -15-酮 （结构式见下）  (21,38,411,511,81,101,111,128,138,141)-13-[(>^heterocyclopropyl)methyl]-11-[[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12, 14- Hexamethyloxy-hetero-6-azetidine fifteenth hospital-15-ketone (see below for structural formula)
Figure imgf000043_0003
Figure imgf000043_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "环乙胺 4mL" , 其余同实施例 14。 中间 获得 0.23g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "cycloethylamine 4 mL", and the rest was the same as in Example 14. 0.23 g of crude product was obtained in the middle to give the title compound.
TLC R产 0.48(二氯甲烷： 甲醇 =7:1)  TLC R yield 0.48 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 632[M+H]  ESI/MS: m/z 632[M+H]
实施例 43 Example 43
(21，38,41，511,81，101 ,111，123,138，1411)-13-[(二乙基氨基)甲基]-11-[ ( 4-二甲基氨基 -3-羟基 -6- 甲基 -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂 环十五烷，15-酮 （结构式见下）  (21, 38, 41, 511, 81, 101, 111, 123, 138, 1411)-13-[(diethylamino)methyl]-11-[(4-dimethylamino-3-hydroxy-6- Methyl-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl- 1-oxo-hetero-6-azacyclopentadecane, 15-ketone (see below for structural formula)
42  42
替换页 （细则第 26条)
Figure imgf000044_0001
Replacement page (Article 26)
Figure imgf000044_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "二乙胺 4mL"， 其余同实施例 14。 中间 获得 0.21g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "diethylamine 4 mL", and the rest was the same as in Example 14. 0.21 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.48(二氯甲烷： 甲醇 =7:1)  TLC Rf = 0.48 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 662[M+H]十  ESI/MS: m/z 662[M+H] 十
实施例 4 Example 4
(211，35，411,51，81 ,101 ,1111，128，138，141 )-13-[(环戊基-氨基)甲基]-11-[ ( 4-二甲基氨基 -3-羟基 -6- 甲基 -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮杂 环十五烷 -15-酮 （结构式见下）  (211,35,411,51,81,101,1111,128,138,141)-13-[(cyclopentyl-amino)methyl]-11-[(4-dimethylamino-3-hydroxyl) -6-methyl-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-six Methyl small oxygen-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000044_0002
Figure imgf000044_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "环戊胺 4mL" , 其余同实施例 14。 中间 获得 0.22g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "cyclopentylamine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.48(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.48 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 662[M+H]+ ESI/MS: m/z 662[M+H] +
实施例 45 Example 45
(211,38,411,511，811,101，111，128,138，1411)-1 [[3，4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4，10,13-四羟基 -13-[(4-甲氧基 -苄基氨基) -甲基 ]-3，5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五焼 -15-酮 （结构式见  (211, 38, 411, 511, 811, 101, 111, 128, 138, 1411)-1 [[3,4,6-Trideoxy-3-(dimethylamino)-indole-0-hexylopyranosyl]oxy] - 2-ethyl-3,4,10,13-tetrahydroxy-13-[(4-methoxy-benzylamino)-methyl]-3,5,8,10,12,14-hexamethyl -1-Oxo-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000044_0003
Figure imgf000044_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "对甲氧基苄胺 4mL"， 其余同实施例 14。 中间获得 0.23g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "p-methoxybenzylamine 4 mL", and the rest was the same as in Example 14. 0.23 g of crude product was obtained in the middle to give the title compound.
TLC R尸 0.45(二氯甲垸： 甲醇 =7:1)  TLC R corpse 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 726[M+H]+ ESI/MS: m/z 726[M+H] +
实施例 46 Example 46
(21，38，41，511，81，101，111，128，133，1411)-1 [[3，4，6-三脱氧-3-(二甲基氨基) -0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -13-[(4-硝基-苄基-氨基) -甲基 ]小氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下） (21,38,41,511,81,101,111,128,133,1411)-1 [[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyryl xylose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(4-nitro-benzyl- Amino)-methyl]sodiumoxy-hetero-6-azetidine-decaquinone-15-one (see below for structural formula)
替换页 （细则第 26条)
Figure imgf000045_0001
Replacement page (Article 26)
Figure imgf000045_0001
将实施例 14中的"叔丁胺 4.5mL"改为使用 "碳酸氢钠 2.0g和对硝基苄胺盐酸盐 4.0g"， 其余同实施例 14。 中间获得 0.23g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "sodium hydrogencarbonate 2.0 g and p-nitrobenzylamine hydrochloride 4.0 g", and the rest was the same as in Example 14. 0.23 g of crude product was obtained in the middle to give the title compound.
TLC R尸 0.45(二氯甲垸： 甲醇 =7:1)  TLC R corpse 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 741 [M+H]+ ESI/MS: m/z 741 [M+H] +
实施例 7 Example 7
(21 ,38，41 ,511581，1011，111，128，138，1411)-13-[(4-氯-苄基氨基)-甲基]-11-[ (4-二甲基氨基 -3-羟基 -6-甲基 -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12,14-六甲基小氧-杂 -6-氮 杂环十五垸 -15-酮 （结构式见下） (21,38,41,511 5 81,1011,111,128,138,1411)-13-[(4-chloro-benzylamino)-methyl]-11-[(4-dimethylamino- 3-hydroxy-6-methyl-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000045_0002
Figure imgf000045_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "对氯苄胺 4mL"， 其余同实施例 14。 中 间获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "p-chlorobenzylamine 4 mL", and the rest was the same as in Example 14. Intermediate was obtained in 0.25 g of crude product to give the title compound.
TLC R产 0.44(二氯甲烷： 甲醇 =7:1)  TLC R yield 0.44 (dichloromethane: methanol = 7:1)
ESI/MS: m z 730[M+H]+ ESI/MS: mz 730[M+H] +
实施例 48 Example 48
(21，38,411,511，811,101 ,1 11 ,128,138，1411)-13-[(3，4-二氟-苄基氨基)甲基]-1 [[3，4,6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12，14-六甲基 -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  (21,38,411,511,811,101,1 11 ,128,138,1411)-13-[(3,4-difluoro-benzylamino)methyl]-1 [[3,4,6-trideoxy-3-(di) Methylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexa Base-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000045_0003
Figure imgf000045_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3,4-二氟苄胺 4mL" ， 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3,4-difluorobenzylamine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.44(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.44 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 732[M+H]+ ESI/MS: m/z 732[M+H] +
实施例 49 Example 49
(2R，3S，4R，5R，8R，10R，l lR，12S，13S,14R)-U-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 替换页 （细则第 26条) 氧基] -2-乙基 -3，4,10，13-四羟基 -3,5,8，10，12,14-六甲基 -13- [(甲基 (吡啶 -4-基)氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五烷 -15-酮 （结构式见下） (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-U-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl] replacement page (Article 26) Oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(methyl(pyridin-4-yl)amino) ) -Methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000046_0001
Figure imgf000046_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "对甲胺基吡啶 4g"， 其余同实施例 14。 中间获得 0.24g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "p-methylaminopyridine 4g", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.44(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.44 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 697[M+H]十  ESI/MS: m/z 697[M+H] 十
实施例 50 Example 50
(211，38，411，51，811，101，111 ,128,133,1411)-13-[(2,6-二氟-苄氨基）甲基]-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5，8,10，12，14-六甲基 -1-氧 -杂 -6-氮杂环十五烷 -15-酮 （结构式见  (211, 38, 411, 51, 811, 101, 111, 128, 133, 1411)-13-[(2,6-difluoro-benzylamino)methyl]-11-[[3,4,6-trideoxy -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 ,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000046_0002
Figure imgf000046_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2,6-二氟苄胺 4mL" ， 其余同实施例 14。 中间获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2,6-difluorobenzylamine 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
TLC ¾=0.44(二氯甲烷： 甲醇 =7:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 732[M+H]  ESI/MS: m/z 732[M+H]
实施例 51 Example 51
(2 ,38,4 ，51，81 51011，111 ,128，138，141 13-[(4-氟-苄氨基)甲基]-11-[ ( 4-二甲基氨基 -3-羟基 -6- 甲基 -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12，14-六甲基 -1-氧-杂 -6-氮杂 环十五烷 -15-酮 （结构式见下） (2,38,4,51,81 5 1011,111,128,138,141 13-[(4-fluoro-benzylamino)methyl]-11-[(4-dimethylamino-3-hydroxy- 6-Methyl-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexa Base-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000046_0003
Figure imgf000046_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "对氟苄胺 4mL" , 其余同实施例 14。 中 间获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "p-fluorobenzylamine 4 mL", and the rest was the same as in Example 14. Intermediate was obtained in 0.25 g of crude product to give the title compound.
TLC ¾=0.44(二氯甲烷： 甲醇 =7:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 714[M+H]  ESI/MS: m/z 714[M+H]
实施例 52 替换页 （细则第 26条) PI S^IUR^IUOIUIIMSS S R S- -氟-苄基-氨基)甲基] -ll-[[3,4，6-三脱氧 -3- (二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12,14-六甲基小氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下） Example 52 Replacement Page (Rule 26) PI S^IUR^IUOIUIIMSS SR S--fluoro-benzyl-amino)methyl]-ll-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-hexipan Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azetidine Pentadec-15-one (see below for structural formula)
Figure imgf000047_0001
Figure imgf000047_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3-氟苄胺 4mL"， 其余同实施例 14。 中间 获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-fluorobenzylamine 4 mL", and the rest was the same as in Example 14. 0.25 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.44(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.44 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 714[M+H]+ ESI/MS: m/z 714[M+H] +
实施例 53 Example 53
(21 ,38,4¾51 ,81，1011,1111,123，138，141 )-13-[(2-氟-苄基-氨基）甲基]-11-[[3，4，6-三脱氧-3-(二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8，10，12，14-六甲基小氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下）  (21,38,43⁄451 ,81,1011,1111,123,138,141 )-13-[(2-fluoro-benzyl-amino)methyl]-11-[[3,4,6-trideoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000047_0002
Figure imgf000047_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "邻氟苄胺 4mL" , 其余同实施例 14。 中 间获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "o-fluorobenzylamine 4 mL", and the rest was the same as in Example 14. Intermediate was obtained in 0.25 g of crude product to give the title compound.
TLC Rf0.44(二氯甲垸： 甲醇 =7:1)  TLC Rf0.44 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 714[M+H]+ ESI/MS: m/z 714[M+H] +
实施例 54 Example 54
21，38，411,51，81 ,101，111，128，138，1411)-13-[(2，4-二氟-苄基-氨基）甲基]-11-[[3，4，6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5,8，10，12,14-六甲基小氧-杂 -6- 氮杂环十五綜 -15-酮 （结构式见下）  21,38,411,51,81,101,111,128,138,1411)-13-[(2,4-difluoro-benzyl-amino)methyl]-11-[[3,4,6 -triptylo-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyloxy-hetero-6-azacyclopentades-15-ketone (see below for structural formula)
Figure imgf000047_0003
Figure imgf000047_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2，4-二氟苄胺 4mL" ， 其余同实施例 14。 中间获得 0.25g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "2,4-difluorobenzylamine 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
4fi  4fi
替换页 （细则第 26条) TLC R尸 0.45(二氯甲烷： 甲醇 =7:1) Replacement page (Article 26) TLC R 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 732[M+H]十  ESI/MS: m/z 732[M+H] 十
实施例 55 Example 55
(2R,3 S,4R,5R,8R, 10R,1 1R,12S, 13S， 14R)- 13-[(2,5-二氟-苄基-氨基)甲基] - 11-[[3，4，6-三脱氧 (2R,3 S,4R,5R,8R, 10R,1 1R,12S, 13S, 14R)- 13-[(2,5-Difluoro-benzyl-amino)methyl] - 11-[[3, 4,6-tripleoxy
-3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8，10,12,14-六甲基小氧-3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 ,14-hexamethyloxygen
-杂 -6-氮杂环十五烷 -15-酮（结构式见下） -hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000048_0001
Figure imgf000048_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2,5-二氟苄胺 4mL" , 其余同实施例 14。 中间获得 0.22g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "2,5-difluorobenzylamine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
Rf=0.45(二氯甲垸： 甲醇 =7:1)  Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 732[M+H]  ESI/MS: m/z 732[M+H]
实施例 56 Example 56
(21，38，411，51，81 ,1011,1111,123,138,141 )-13-[(3，5-二氟-苄基-氨基)甲基]-11-[[3，4，6-三脱氧 (21, 38, 411, 51, 81, 1011, 1111, 123, 138, 141)-13-[(3,5-difluoro-benzyl-amino)methyl]-11-[[3,4,6-trideoxy
-3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5，8，10,12，14-六甲基小氧-3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 ,14-hexamethyloxygen
-杂 -6-氮杂环十五院 -15-酮 （结构式见下） -hetero-6-nitrogen heterocyclic fifteenth hospital -15-ketone (see below for structural formula)
Figure imgf000048_0002
Figure imgf000048_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3，5-二氟苄胺 4mL" ， 其余同实施例 14。 中间获得 0.24g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3,5-difluorobenzylamine 4 mL", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
TLC R尸 0.45(二氯甲垸： 甲醉 =7:1)  TLC R corpse 0.45 (dichloromethane: A drunk = 7:1)
ESI/MS: m/z 732[M+H]  ESI/MS: m/z 732[M+H]
实施例 57 Example 57
(211，33,411,5] ,81 ,1011，111 ,128,138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基) -0-己吡喃木糖基] 氧基] -2-乙基 -13-[4-(4-氟-苯基) -哌嗪 -1-基-甲基] -3,4,10,13-四羟基 -3，5，8，10,12，14-六甲基小氧- 杂 -6-氮杂环十五垸 -15-酮 （结构式见下）  (211,33,411,5],81,1011,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexylopyranosyl]oxy ]-2-Ethyl-13-[4-(4-fluoro-phenyl)-piperazin-1-yl-methyl]-3,4,10,13-tetrahydroxy-3,5,8,10 ,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
47 47
替换页 （细则第 26条)
Figure imgf000049_0001
Replacement page (Article 26)
Figure imgf000049_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "4.0g NaHC03和 1-(4-氟苯基)哌嗪盐酸盐 4.0g"， 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。 The "tert-butylamine 4.5 mL" in Example 14 was changed to use "4.0 g of NaHC0 3 and 1-(4-fluorophenyl)piperazine hydrochloride 4.0 g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC R产 0.45(二氯甲垸： 甲醇 =7:1)  TLC R yield 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 769[M+H]十  ESI/MS: m/z 769[M+H] 十
实施例 38 Example 38
(2R，3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-三氟甲基-苄氨基)甲基] -11-[[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5，8，10，12,14-六甲基 -1-氧 -杂 -6-氮杂环十五垸 -15-酮（结构式见下）  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-trifluoromethyl-benzylamino)methyl]-11-[[[3,4, 6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 ,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000049_0002
Figure imgf000049_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "邻三氟甲基苄胺 4mL"， 其余同实施例 14。 中间获得 0.27g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "o-trifluoromethylbenzylamine 4 mL", and the rest was the same as in Example 14. 0.27 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 764[M+H]+ ESI/MS: m/z 764[M+H] +
实施例 59 Example 59
2 ,33,41^51 ,81^10¾1111,123,138,141 )-13-[(4-三氟甲基-苄基-氨基)甲基] -11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8，10,12，14-六甲基小氧 -杂 -6-氮杂环十五垸 -15-酮 （结构式见下）  2,33,41^51 ,81^103⁄41111,123,138,141 )-13-[(4-Trifluoromethyl-benzyl-amino)methyl]-11-[[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyloxy-hetero-6-azetidine, heptadecane-15-one (see below for structural formula)
Figure imgf000049_0003
Figure imgf000049_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "对三氟甲基苄胺 4mL"， 其余同实施例 The "t-butylamine 4.5 mL" in Example 14 was changed to use "p-trifluoromethylbenzylamine 4 mL", and the rest of the same examples.
14。 中间获得 0.26g粗品， 最终得标题化合物。 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲烷： 甲醇 =7:1)  TLC 3⁄4 = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 764[M+H]+ ESI/MS: m/z 764[M+H] +
实施例 60 替换页 （细则第 26条) (2R,3S，4R,5R，8R,10R，l lR，12S,13S,14R)-13-[(3-三氟甲基-苄基-氨基）甲基] -l l-[[3,4,6-三脱氧 -3-(二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基小氧 -杂 -6-氮杂环十五垸 -15-酮 （结构式见下） Example 60 Replacement Page (Rule 26) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3-trifluoromethyl-benzyl-amino)methyl]-l l-[[3, 4,6-trideoxy - 3 - (dimethylamino) -β-D- xylopyranosyl hexyl] oxy] -2-ethyl-3,5-tetrahydroxy--3,4,10,13- , 8,10,12,14-hexamethyloxy-hetero-6-nitrohecyclopentadecane-15-one (see below for structural formula)
Figure imgf000050_0001
Figure imgf000050_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "间三氟甲基苄胺 4mL"， 其余同实施例 14。 中间获得 0.24g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "m-trifluoromethylbenzylamine 4 mL", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 764[M+H]十  ESI/MS: m/z 764[M+H] 十
实施例 61 Example 61
2R,3S,4R,5R,8R,10R,11R,12S,13S,14R) -13-{[乙基 -(2-氟-苯基) -氨基] -甲基 }-U-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧 -杂 -6-氮杂环十五垸 -15-酮 （结构式见下）  2R,3S,4R,5R,8R,10R,11R,12S,13S,14R) -13-{[ethyl-(2-fluoro-phenyl)-amino]-methyl}-U-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 ,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000050_0002
Figure imgf000050_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "碳酸氢钠 2.0g和 N- (2-氟苯基） 乙胺盐 酸盐 4.0g"， 其余同实施例 14。 中间获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "sodium hydrogencarbonate 2.0 g and N-(2-fluorophenyl)ethylamine hydrochloride 4.0 g", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 728[M+H]+ ESI/MS: m/z 728[M+H] +
实施例 62 Example 62
(2R，3S，4R,5R，8R,10R,l lR,12S，13S,14R)-13-{ [乙基 -(3-氟-苯基) -氨基] -甲基 }-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧 -杂 -6-氮杂环十五垸 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{ [ethyl-(3-fluoro-phenyl)-amino]-methyl}-11-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 ,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000050_0003
Figure imgf000050_0003
49  49
替换页 （细则第 26条) 将实施例 14中的 "叔丁胺 4.5mL"改为使用 "碳酸氢钠 2.0g和 N- (3-氟苯基） 乙胺盐 酸盐 4.0g"， 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。 Replacement page (Article 26) The "tert-butylamine 4.5 mL" in Example 14 was changed to use "sodium hydrogencarbonate 2.0 g and N-(3-fluorophenyl)ethylamine hydrochloride 4.0 g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC Rj=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rj=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 728[M+H]十  ESI/MS: m/z 728[M+H] 十
实施例 63 Example 63
(21 ，38,41 ，51 ，81 ，101 ，111 ，123，133,141 )-13-[(2-氟-6-三氟甲基-苄基-氨基)甲基]-11-[[3，4，6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-氧- (21, 38, 41, 51, 81, 101, 111, 123, 133, 141)-13-[(2-fluoro-6-trifluoromethyl-benzyl-amino)methyl]-11-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-oxo-
2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五院 -15-酮（结构式见下） 2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azetidine fifteenth hospital-15-ketone (see below for structural formula)
Figure imgf000051_0001
Figure imgf000051_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-氟 -6-三氟甲基苄胺 4.0g"， 其余同实施 例 14。 中间获得 0.24g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-fluoro-6-trifluoromethylbenzylamine 4.0g", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 782[M+H]+ ESI/MS: m/z 782[M+H] +
实施例 64 Example 64
(2 38，4¾51 ,8]^，1011,111 ,128,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12,14-六甲基 -13- [(甲基- (吡啶 -3-基） -氨基) -甲基 ]-1- 氧-杂 -6-氮杂环十五烷 -15-酮 （结构式见下） (2 38,43⁄451 ,8]^,1011,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyryl xylose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(methyl-(pyridine-3- -amino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000051_0002
Figure imgf000051_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3- (N-甲胺基） 吡啶 4.0g"， 其余同实施 例 14。 中间获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-(N-methylamino)pyridine 4.0g", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲烷： 甲醇 =7:1)  TLC 3⁄4 = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 697[M+H]十  ESI/MS: m/z 697[M+H] 十
实施例 65 Example 65
(2R,3S，4R,5R,8R,10R,l lR，12S,13S,14R)- -13-[(4-羟基 -3-甲氧基-苄基-氨基) - 甲基] -11-[[3,4，6- 三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12,14-六甲基 小氧-杂 _6·氮杂环十五烧—15—酮 （结构式见下） (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)--13-[(4-hydroxy-3-methoxy-benzyl-amino)-methyl]-11- [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]yl]-2-ethyl-3,4,10,13-tetrahydroxy- 3,5,8,10,12,14-hexamethyloxy-hetero- 6 -nitrogen heterocycle fifteen- 15-ketone (see below for structural formula)
50 50
替换页 （细则第 26条)
Figure imgf000052_0001
Replacement page (Article 26)
Figure imgf000052_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "4-羟基 -3-甲氧基 -苄胺 4.0mL"， 其余同实 施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "4-hydroxy-3-methoxy-benzylamine 4.0 mL", and the rest was the same as Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲烷： 甲醇 =7:1)  TLC Rf = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 742[M+H]+ ESI/MS: m/z 742[M+H] +
实施例 66 Example 66
(2R,3S,4R,5R,8R,10R,11 ,12S,13S,14R)-13- {苯并 [1,3]二氧 -5-基-氨基-甲基) } -11-[[3，4，6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10，12,14-六甲基小 氧-杂 -6-氮杂环十五垸 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,11,12S,13S,14R)-13- {Benzo[1,3]dioxo-5-yl-amino-methyl) } -11-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 ,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000052_0002
Figure imgf000052_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "胡椒胺 4mL" ， 其余同实施例 14。 中间 获得 0.27g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "pepperamine 4 mL", and the rest was the same as in Example 14. 0.27 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲烷： 甲醇 =7:1)  TLC Rf = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 726[M+H]+ ESI/MS: m/z 726[M+H] +
实施例 67 Example 67
21，33，41 )51 ,81，101，111 ,128，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基) 0-己吡喃木糖基] 氧基] -2-乙基 -3，4，10,13-四羟基 -3，5，8，10,12,14-六甲基 -13-[(3-甲氧基-苄基-氨基) -甲基 ]小氧-杂 -6-氮杂环十五垸 -15-酮 （结构式见下） 21,33,41 ) 51 ,81,101,111 ,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino) 0-hexanlopyranosyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(3-methoxy-benzyl- Amino)-methyl]sodiumoxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000052_0003
Figure imgf000052_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 3-甲氧基苄胺 4mL"， 其余同实施例 14。 中间获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use 3-methoxybenzylamine 4 mL", and the remainder was the same as in Example 14. 0.25 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 726[M+H]  ESI/MS: m/z 726[M+H]
51  51
替换页 （细则第 26条) 实施例 68 Replacement page (Article 26) Example 68
2R，3S，4R，5R，8R,10R，l lR，12S，13S,14R)-13-[(2-甲氧基 -苄基氨基) -甲基 ]-l l-[[3,4，6-三脱氧 -3- (二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5，8,10，12,14-六甲基 -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-methoxy-benzylamino)-methyl]-l l-[[3,4, 6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 ,10,12,14-hexamethyl-1-oxo-6-nitrozacyclopentadecane-15-one (see below for structural formula)
Figure imgf000053_0001
Figure imgf000053_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-甲氧基苄胺 4mL" ， 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-methoxybenzylamine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC RH).45(二氯甲垸： 甲醇 =7:1)  TLC RH).45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 726[M+H]+ ESI/MS: m/z 726[M+H] +
实施例 69 Example 69
2R,3S,4R55R,8R,10R,11R,12S,13S,14R)-13- ((吡啶 -2-基-氨基） -甲基 )-11-[[3,4,6-三脱氧 -3- (二 甲基氨基)甲基 -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8，10，12,14-六甲基 -1-氧- 杂 -6-氮杂环十五烷 -15-酮 （结构式见下） 2R,3S,4R 5 5R,8R,10R,11R,12S,13S,14R)-13-((pyridin-2-yl-amino)-methyl)-11-[[3,4,6-tripleoxy -3- (Dimethylamino)methyl-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 ,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000053_0002
Figure imgf000053_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-氨基吡啶 4.0g" , 其余同实施例 14。 中 间获得 0.24g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-aminopyridine 4.0g", and the rest was the same as in Example 14. In the middle, 0.24 g of crude product was obtained, which gave the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 683[M+H]十  ESI/MS: m/z 683[M+H] 十
实施例 70 Example 70
(2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[ (2-甲氧基 -乙基氨基）甲基] -11-[[3，4，6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8，10,12，14-六甲基 -1- 氧-杂 -6-氮杂环十五垸 · 15-酮 （结构式  (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(2-methoxy-ethylamino)methyl]-11-[[3,4,6 -triptylo-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (structural formula)
Figure imgf000053_0003
Figure imgf000053_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-甲氧基乙胺 4mL"， 其余同实施例 14。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-methoxyethylamine 4 mL", and the rest was the same as in Example 14.
替换页 （细则第 26条) 中间获得 0.23g粗品， 最终得标题化合物。 Replacement page (Article 26) 0.23 g of crude product was obtained in the middle to give the title compound.
TLC RfK).45(二氯甲垸： 甲醇 =7:1)  TLC RfK).45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 664[M+H]+ ESI/MS: m/z 664[M+H] +
实施例 71 Example 71
(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[ (2-羟基 -N-甲基-乙氨基）甲基] -11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5，8，10，12,14-六甲基 -1-氧 -杂 -6-氮杂环十五烷 -15-酮 （结构式 (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-hydroxy-N-methyl-ethylamino)methyl]-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (structural formula
Figure imgf000054_0001
Figure imgf000054_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-羟基 -N-甲基乙胺 4mL" , 其余同实施 例 14。 中间获得 0.22g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "2-hydroxy-N-methylethylamine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 664[M+H]十  ESI/MS: m/z 664[M+H] 十
实施例 n Example n
(21，33,411,51 ,81 ,101，111 ,123,133,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-{ [(吡啶 -2-基-甲基) -氨基] -甲基 }-1-氧- 杂 -6-氮杂环十五院 -15-酮 （结构式  (21,33,411,51,81,101,111,123,133,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyranidyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{[(pyridin-2-yl-methyl) )-amino]-methyl}-1-oxo-hetero-6-azetidine fifteenth hospital-15-one (structural formula)
Figure imgf000054_0002
Figure imgf000054_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-甲基-氨基吡啶 4.0g"， 其余同实施例 14。 中间获得 0.21g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-methyl-aminopyridine 4.0g", and the rest was the same as in Example 14. 0.21 g of crude product was obtained in the middle to give the title compound.
Rj=0.45(二氯甲烷： 甲醇 =7:1)  Rj = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 697[M+H]  ESI/MS: m/z 697[M+H]
实施例 73 Example 73
(2R,3S，4R,5R,8R，10R,1 lR,12S,13S,14R)-13-[ (羟基氨基）甲基] -11-[[3，4，6-三脱氧 -3- (二甲基氨 基) -β-D-S吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环 十五院 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(hydroxyamino)methyl]-11-[[3,4,6-trideoxy-3- ( Dimethylamino)-β-DS-pyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl -1-Oxo-hetero-6-azetidine fifteenth hospital-15-ketone (see below for structural formula)
Figure imgf000054_0003
Figure imgf000054_0003
将实施例 14中的 "叔丁胺 4.5mL"改 用 "羟胺 4.0g"， 其余同实施例 14。 中间获得 替换页 （细则第 26条) 0.21g粗品， 最终得标题化合物。 The "tert-butylamine 4.5 mL" in Example 14 was changed to "hydroxylamine 4.0 g", and the rest was the same as in Example 14. Get a replacement page in the middle (Article 26) 0.21 g of crude product, the title compound was obtained.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 622[M+H]+ ESI/MS: m/z 622[M+H] +
实施例 74 Example 74
(2R,3S,4R,5R，8R，10R，l lR,12S，13S，14R)-13-{[(2-羟基-乙基) -氨基] -甲基 }-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10，12,14-六甲基小氧 -杂 -6-氮杂环十五垸 -15-酮 （结构式 (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[(2-hydroxy-ethyl)-amino]-methyl}-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (structural formula
Figure imgf000055_0001
Figure imgf000055_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-羟基乙胺 4mL"， 其余同实施例 14。 中 间获得 0.20g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-hydroxyethylamine 4 mL", and the rest was the same as in Example 14. A 0.20 g crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲烷： 甲醇 =7:1)  TLC Rf = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 650[M+H]十  ESI/MS: m/z 650 [M+H] ten
实施例 5 Example 5
(2 ,33,4!，51 ,81，101，111，123，133，1411)-11-[[3,4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -13-{[(3-氟-苯基) -甲基-氨基] -甲基 }-3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基小氧- 杂 -6-氮杂环十五烷 -15-酮 （结构式  (2,33,4!,51,81,101,111,123,133,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl Pyranopyranyl]oxy]-2-ethyl-13-{[(3-fluoro-phenyl)-methyl-amino]-methyl}-3,4,10,13-tetrahydroxy-3 ,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (structural formula
Figure imgf000055_0002
Figure imgf000055_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3-氟 -N-甲基苯胺 4mL" , 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-fluoro-N-methylaniline 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲烷： 甲醇 =7:1)  TLC 3⁄4 = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 713[M+H]  ESI/MS: m/z 713[M+H]
实施例 76 Example 76
(2R,3S，4R，5R，8R,10R，l lR，12S,13S，14R)-13-[(6-氯 -吡啶 -3-基-氨基) -甲基 ]-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基】-2-乙基 -3,4，10，13-四羟基 -3，5，8，10,12,14-六甲基 -1-氧 -杂 -6-氮杂环十五垸 -15-酮 （结构  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(6-chloro-pyridin-3-yl-amino)-methyl]-11-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 ,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (structure
Figure imgf000055_0003
Figure imgf000055_0003
替换页 （细则第 26条) 将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3-氨基 -6-氯吡啶 4mL"， 其余同实施例 14。 中间获得 0.22g粗品， 最终得标题化合物。 Replacement page (Article 26) The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-amino-6-chloropyridine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲烷： 甲醇 =7:1)  TLC 3⁄4 = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 714[M+H]十  ESI/MS: m/z 714[M+H] 十
实施例 77 Example 77
(21 ，38,41 ,51 ,811，101 ，111 ，128,138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10，13-四羟基 -13-[(4-羟基-正丁基氨基) -甲基 ]-3,5,8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五院 -15-酮 （结构式见  (21,38,41,51,811,101,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyranidyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(4-hydroxy-n-butylamino)-methyl]-3,5,8,10,12,14 -hexamethyl-1-oxo-hetero-6-azetidine fifteenth hospital-15-ketone (see structure formula
Figure imgf000056_0001
Figure imgf000056_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "4-羟基正丁胺 4mL" ， 其余同实施例 14。 中间获得 0.25g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "4-hydroxy-n-butylamine 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 678[M+H]十  ESI/MS: m/z 678[M+H] 十
实施例 78 Example 78
4-{(21 ，35，411,511,811,101 ,111 ，123，138,1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基)- -0-己吡喃木糖 基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -15-酮小氧-杂 -6-氮杂环十五垸 -13-基- 甲基] -氨基 }-甲基-苯甲酸（结构式 4-{(21 , 35,411,511,811,101 ,111 ,123,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)- -0-hexyranopyranosyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one small oxygen-hetero-6-nitrogen heterocycle Fifteen 垸-13-yl-methyl]-amino}-methyl-benzoic acid (structural formula
Figure imgf000056_0002
Figure imgf000056_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "4-氨甲基苯甲酸 4.0g"， 其余同实施例 14。 中间获得 0.24g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "4-aminomethylbenzoic acid 4.0 g", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
TLC Rf0.45(二氯甲烷： 甲醇 =7:1)  TLC Rf 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 740[M+H]十  ESI/MS: m/z 740[M+H] 十
实施例 79 Example 79
(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13- (2-烯丙基-氨基） -甲基 -11-[[3，4，6-三脱氧 -3- (二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-(2-allyl-amino)-methyl-11-[[3,4,6-trideoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
55 55
替换页 （细则第 26条)
Figure imgf000057_0001
Replacement page (Article 26)
Figure imgf000057_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-烯丙胺 4mL"， 其余同实施例 14。 中间 获得 0.24g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "2-allylamine 4 mL", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲烷： 甲醇 =7:1)  TLC 3⁄4 = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 646[M+H]  ESI/MS: m/z 646[M+H]
实施例 80 Example 80
(2R,3S，4R,5R,8R，10R，l lR,12S,13S,14R)-13-{[(3-氨基 -1,4,4-三甲基 -环己基-甲基)-氨基] -甲 基 }-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5,8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮（结构式见下） ( 2 R,3S, 4 R,5R,8R,10R,l lR,12S,13S,14R)-13-{[(3-amino-1,4,4-trimethyl-cyclohexyl-methyl) -amino]-methyl}-11-[[3,4,6-tripodeoxy-3-(dimethylamino)-β-D-hexyranopyranyl]oxy]-2-ethyl- 3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000057_0002
Figure imgf000057_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3-氨基 -1，4，4-三甲基-环己基 -甲胺 4mL"， 其余同实施例 14。 中间获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-amino-1,4,4-trimethyl-cyclohexyl-methylamine 4 mL", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 760[M+H]十  ESI/MS: m/z 760[M+H] 十
实施例 81 Example 81
(211，33，41，511,81 ,101，111，128，133,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3，4,10，13-四羟基 -13-{[2-(2-羟基-乙基-氨基) -乙基氨基] -甲基 }-3,5,8,10，12,14-六 甲基 -1-氧-杂 -6-氮杂环十五院 -15-  (211,33,41,511,81,101,111,128,133,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-{[2-(2-hydroxy-ethyl-amino)-ethylamino]-methyl}-3 ,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-nitrogen heterocycle
Figure imgf000057_0003
Figure imgf000057_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2- (2-羟基） 乙氨基乙胺 4mL"， 其余同 实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "2-(2-hydroxy)ethylaminoethylamine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC Rj=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rj=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 693[M+H]+ ESI/MS: m/z 693[M+H] +
实施例 82 Example 82
(211,38，41，51 ,811，101，111 ,128,138,141 )-13-[(2-氯-4-甲氧-苄基氨基)-甲基]-11-[[3,4,6-三 脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5,8,10,12,14-六甲基  (211, 38, 41, 51, 811, 101, 111, 128, 138, 141)-13-[(2-chloro-4-methoxy-benzylamino)-methyl]-11-[[3,4,6- Triphos-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 ,12,14-hexamethyl
56  56
替换页 （细则第 26条) -1-氧-杂 -6-氮杂环十五烷 -15-酮 （结构式见下) Replacement page (Article 26) -1-Oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000058_0001
Figure imgf000058_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "碳酸氢钠 3.0g和 2-氯 -4-甲氧基苄胺盐酸 盐 4.0g"， 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "sodium hydrogencarbonate 3.0 g and 2-chloro-4-methoxybenzylamine hydrochloride 4.0 g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC 1尸0.45(二氯甲垸： 甲醇 =7:1)  TLC 1 corpse 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z760[M+H]  ESI/MS: m/z760[M+H]
实施例 83 Example 83
(2R3S4R,5R,8R，10R，11R12S 13S14R)-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，1214-六甲基 -13- [( 甲基 -3-苯基-丙基-氨基) -甲基 ]-1- 氧-杂 -6-氮杂环十五烷 -15-酮（结  (2R3S4R,5R,8R,10R,11R12S 13S14R)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy] - 2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,1214-hexamethyl-13-[(methyl-3-phenyl-propyl-amino)-methyl ]-1-Oxo-hetero-6-azacyclopentadecane-15-one (knot)
Figure imgf000058_0002
Figure imgf000058_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 " 1-甲基 -3-苯基丙胺 4mL"， 其余同实施例 14。 中间获得 0.22g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "1-methyl-3-phenylpropylamine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
TLC RH).45(二氯甲垸： 甲醇 =7:1)  TLC RH).45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 739[M+H]  ESI/MS: m/z 739[M+H]
实施例 84 Example 84
(21 3841151 ,81,1011,111 128138141)-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3581012,14-六甲基 -13-哌嗪 -1-基 -甲基 -1-氧-杂 -6-氮杂环十五 垸 -15-酮 （结构式见下）  (21 3841151,81,1011,111 128138141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-l-hexyranosyl]oxy] -2 -ethyl-3,4,10,13-tetrahydroxy-3581012,14-hexamethyl-13-piperazin-1-yl-methyl-1-oxo-hetero-6-azacyclopentadecane- 15-ketone (see below for structural formula)
Figure imgf000058_0003
Figure imgf000058_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "哌嗪 4g"， 其余同实施例 14。 中间获得 0.21g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "piperazine 4g", and the rest was the same as in Example 14. 0.21 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z675[M+H]  ESI/MS: m/z675[M+H]
实施例 85 替换页 （细则第 26条) (2R,3S,4R,5R,8R10R,11R,12S 13S,14R)-11-[[3,46-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3,41013-四羟基 -3,5,810,12,14-六甲基 -13-{ [(吡啶 -4-基-甲基) -氨基] -甲基 }小氧- 杂 -6-氮杂环十五浣 -15-酮（结构式 Example 85 Replacement Page (Rule 26) (2R,3S,4R,5R,8R10R,11R,12S 13S,14R)-11-[[3,46-Trideoxy-3-(dimethylamino)-β-D-hexyranopyranosyl] oxy] -2-ethyl -3,41013- four-hydroxy-3, 5, 810,1 2, 14 six-13- {[(pyridin-4-yl - methyl) - amino] - methyl Small oxygen-hetero-6-nitrohecyclopentadecane-15-one (structural formula)
Figure imgf000059_0001
Figure imgf000059_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "4-甲氨基吡啶 4g" , 其余同实施例 14 中间获得 0.23g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "4-methylaminopyridine 4g", and the residue obtained in the same manner as in Example 14 was obtained to give the title compound.
TLC R尸 0.45(二氯甲烷： 甲醇 =7:1)  TLC R 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z697[M+H]  ESI/MS: m/z697[M+H]
实施例 86 Example 86
(2R,3S,4 ,5R,8R, 1 OR, 11 R, 12S, 13S, 14R)- 13-{[(3-氯 -吡啶 -4-基） 甲基氨基]甲基 }-13-{[(2-羟基- 乙基) -甲基-氨基] -甲基 }-11-[[346-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -358,10,12,14-六 五烷 -15-酮 （结构式见下）  (2R,3S,4,5R,8R, 1 OR, 11 R, 12S, 13S, 14R)- 13-{[(3-chloro-pyridin-4-yl)methylamino]methyl}-13-{ [(2-hydroxy-ethyl)-methyl-amino]-methyl}-11-[[346-trideoxy-3-(dimethylamino)-β-D-hexyranose]oxy Benzyl]-2-ethyl-3,4,10,13-tetrahydroxy-358,10,12,14-hexapentane-15-one (see below for structural formula)
Figure imgf000059_0002
Figure imgf000059_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "4-甲氨基 -3-氯吡啶 4g" , 其余同实施例 14。 中间获得 0.21g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "4-methylamino-3-chloropyridine 4g", and the rest was the same as in Example 14. 0.21 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 732[M+H]  ESI/MS: m/z 732[M+H]
实施例 87 Example 87
1^-{(2113841 51^81 101 111 128138141)-11-[[34,6-三脱氧-3-(二甲基氨基 卩-0-己吡喃木糖 基]氧基] -2-乙基 -341013-四羟基 -358101214-六甲基 -15-酮小氧-杂 -6-氮杂环十五烷 -13-基- 甲基 }-222-三氟-乙酰胺 （结构式见下）  1^-{(2113841 51^81 101 111 128138141)-11-[[34,6-Trideoxy-3-(dimethylaminoindole-0-hexylpyranosyl)oxy]-2-B Base-341013-tetrahydroxy-358101214-hexamethyl-15-one small oxygen-hetero-6-azacyclopentadecane-13-yl-methyl}-222-trifluoro-acetamide (see below for structural formula)
Figure imgf000059_0003
Figure imgf000059_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "三氟乙酰胺 4g" ， 其余同实施例 14。 中 间获得 0.24g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "trifluoroacetamide 4g", and the rest was the same as in Example 14. In the middle, 0.24 g of crude product was obtained, which gave the title compound.
58 58
替换页 （细则第 26条) TLC Rf=0.45(二氯甲烷： 甲醇 =7:1) Replacement page (Article 26) TLC Rf = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 702[M+H]十  ESI/MS: m/z 702[M+H] 十
(2R，3S，4R，5R，8R，10R,l lR，12S,13S，14R)-13-{[(2-氯-吡啶 -4-基-甲基) -氨基] -甲基 }-l l-[[3,4,6-三 脱氧 -3-(二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮 （结 (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[(2-chloro-pyridin-4-yl-methyl)-amino]-methyl}-l L-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13- Tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-6-nitrozacyclopentadecane-15-one (knot)
Figure imgf000060_0001
Figure imgf000060_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "4-甲氨基 -6-氯吡啶 4g"， 其余同实施例 14。 中间获得 0.24g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "4-methylamino-6-chloropyridine 4g", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲烷： 甲醇 =7:1)  TLC 3⁄4 = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 732[M+H]  ESI/MS: m/z 732[M+H]
实施例 89 Example 89
(2R,3S,4R,5R,8R, 10R,11R,12S, 13S, 14R)-11 -[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3，4,10，13-四羟基 -13- [(正戊基-氨基) -甲基 ]-3，5,8,10,12，14-六甲基 -1-氧-杂 -6-氮杂 环十五院 -15-酮（结构式见下）  (2R,3S,4R,5R,8R, 10R,11R,12S, 13S, 14R)-11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexidyl Erkisyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(n-pentyl-amino)-methyl]-3,5,8,10,12, 14-hexamethyl-1-oxo-hetero-6-azetidine fifteenth hospital-15-ketone (see below for structural formula)
Figure imgf000060_0002
Figure imgf000060_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "正戊胺 4mL"， 其余同实施例 14。 中间 获得 0.22g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "n-pentylamine 4 mL", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 676[M+H]  ESI/MS: m/z 676[M+H]
实施例 9 Example 9
(211,38,411，51 ,81 ,101，1111，128,138,141 )-13-[(111-苯并咪唑-2-基-氨基)-甲基]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8,10,12，14-六甲基小氧 -杂 -6-氮杂环十五烷 -15-酮（结构  (211, 38, 411, 51, 81, 101, 1111, 128, 138, 141)-13-[(111-benzimidazol-2-yl-amino)-methyl]-11-[[3,4,6-trideoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (structure
Figure imgf000060_0003
Figure imgf000060_0003
59  59
替换页 （细则第 26条) 将实施例 14中的 "叔丁胺 4.5mL"改为使用 "1H-苯并 2-氨基咪唑 4g"， 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。 Replacement page (Article 26) The "t-butylamine 4.5 mL" in Example 14 was changed to use "1H-benzo-2-aminoimidazole 4g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z722[M+H]  ESI/MS: m/z722[M+H]
实施例 91 Example 91
(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R) -13-(Ν,Ν'-二甲基 -肼基 -甲基 )-11-[[3,4，6-三脱氧 -3- (二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12，14-六甲基 -1-氧-杂 -6- 氮杂环十五烷 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R) -13-(Ν,Ν'-dimethyl-indolyl-methyl)-11-[[3,4,6 -triptylo-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000061_0001
Figure imgf000061_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "Ν,Ν'-二甲基-肼 4mL"， 其余同实施例 14 中间获得 0.23g粗品， 最终得标题化合物。 Example 14 "4.5 mL of tert-butylamine" to use "Ν, Ν'- dimethyl - 4 mL hydrazine", to obtain 0.23 g of crude product remaining with the intermediate of Example 14, to give the final title compound.
TLC Rf=0.45(二氯甲烷： 甲醇 =7:1)  TLC Rf = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z649[M+H]+ ESI/MS: m/z649[M+H] +
实施例 92 Example 92
(21,3841 51 ,811101,111 128,138141)-13-[(2,6-二氟-4-甲氧-苄基-氨基)甲基]-11-[[346-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -341013-四羟基 -358101214-六甲基小 氧-杂 -6-氮杂环十五烷 -15-酮 （结构 (21,3841 51 ,811101,111 128,138141)-13-[(2,6-difluoro-4-methoxy-benzyl-amino)methyl]-11-[[346-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-341013-tetrahydroxy-358101214-hexamethyloxy-hetero-6-azacyclopentadecane -15-ketone (structure
Figure imgf000061_0002
Figure imgf000061_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2,6-二氟 -4-甲氧基苄胺 4mL"， 其余同实 施例 14。 中间获得 0.24g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2,6-difluoro-4-methoxybenzylamine 4 mL", and the rest was the same as Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z762[M+H]  ESI/MS: m/z762[M+H]
实施例 93 Example 93
(21 33，41 51，81 10 1111，123，13814] )-11-[[3，4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -13-{[2-(2-羟基-乙氧基) -乙基氨基] -甲基 }-3,5810,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮 （结构式见下）  (21 33,41 51,81 10 1111,123,13814] )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexylopyranosyl] Oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-{[2-(2-hydroxy-ethoxy)-ethylamino]-methyl}-3,5810,12 ,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
60 60
替换页 （细则第 26条)
Figure imgf000062_0001
Replacement page (Article 26)
Figure imgf000062_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "二甘醇胺 4mL"， 其余同实施例 14。 中 间获得 0.20g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "diethylene glycolamine 4 mL", and the rest was the same as in Example 14. A 0.20 g crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 694[M+H]+ ESI/MS: m/z 694[M+H] +
实施例 94 Example 94
(2R,3S4R,5R,8R,10RllR,12S,13S 14R)-13-[(2-氯 -乙基氨基) -甲基 ]-11-[[3,4,6-三脱氧 -3- (二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,1013-四羟基 -3,5,810,1214-六甲基 -1-氧-杂 -6-氮 杂环十五浣 -15-酮 （结构式见下）  (2R,3S4R,5R,8R,10RllR,12S,13S 14R)-13-[(2-Chloro-ethylamino)-methyl]-11-[[3,4,6-trideoxy-3- ( Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,1013-tetrahydroxy-3,5,810,1214-hexamethyl-1-oxo- -6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000062_0002
Figure imgf000062_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-氯乙胺盐酸盐 4.0g"，其余同实施例 14 中间获得 0.21g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-chloroethylamine hydrochloride 4.0 g", and the residue obtained in the same manner as in Example 14 was obtained.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 668[M+H]  ESI/MS: m/z 668[M+H]
实施例 95 Example 95
2- {(21^38,41151 811,101 111 ,1281381411)-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖 基]氧基] -2-乙基 -341013-四羟基 -3,5810,12,14-六甲基 -15-酮小氧-杂 -6-氮杂环十五垸 -13-基- 甲基] -氨基 } -丁酸（结构式见下）  2- {(21^38,41151 811,101 111 ,1281381411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy ]-2-Ethyl-341013-tetrahydroxy-3,5810,12,14-hexamethyl-15-oneoxy-hetero-6-azetidine,decafluoro-13-yl-methyl]-amino } - Butyric acid (see below for structural formula)
Figure imgf000062_0003
Figure imgf000062_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-氨基丁酸 4.0g"， 其余同实施例 14。 中 间获得 0.22g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-aminobutyric acid 4.0g", and the rest was the same as in Example 14. 0.22 g of crude product was obtained in the middle to give the title compound.
TLC Rj=0.45(二氯甲烷： 甲醇 =7:1)  TLC Rj = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z692[M+H]  ESI/MS: m/z692[M+H]
实施例 96 Example 96
3- {(211,38411,511,811,1(^111 ,128,138,141)-11-[[3,4,6-三脱氧-3-(二甲基氨基)-3-0-己吡喃木糖 基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -15-酮 -1-氧-杂 -6-氮杂环十五垸 -13-基- 甲基] -氨基 } -丙酸 （结构式见下） 替换页 （细则第 26条)
Figure imgf000063_0001
3- {(211,38411,511,811,1(^111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyranidyl) ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one-1-oxo-hetero-6-nitrogen Heterocyclic fifteen 垸-13-yl-methyl]-amino}-propionic acid (see structure below) Replacement page (Article 26)
Figure imgf000063_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "β-氨基丙酸胺 4.0g" , 其余同实施例 14。 中间获得 0.24g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "β-aminopropionic acid amine 4.0g", and the rest was the same as in Example 14. 0.24 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 678[M+H]  ESI/MS: m/z 678[M+H]
实施例 97 Example 97
(21^38,41，51 ,811,101，111，128,138，1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -13-[(4-氟 -2-硝基 -苯基氨基) -甲基 ]-3,4,10，13-四羟基 -3,5,8,10,12,14-六甲基小氧- 杂 -6-氮杂环十五垸 -15-酮 （结构式见  (21^38,41,51,811,101,111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyranose ]oxy]-2-ethyl-13-[(4-fluoro-2-nitro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy-3,5,8,10 ,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000063_0002
Figure imgf000063_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-硝基 -4-氟苯胺 4g"， 其余同实施例 14。 中间获得 0.25g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-nitro-4-fluoroaniline 4g", and the rest was the same as in Example 14. A crude product of 0.25 g was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 745[M+H]+ ESI/MS: m/z 745[M+H] +
¾ 3⁄4
(2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(4-溴 -2-氟 -苯基氨基） -甲基] -11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8，10，12,14-六甲基小氧 -杂 -6-氮杂环十五烷 -15-酮 （结构式  (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(4-bromo-2-fluoro-phenylamino)-methyl] -11-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 ,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (structural formula
Figure imgf000063_0003
Figure imgf000063_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-氟 -4溴苯胺 4g" , 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-fluoro-4-bromoaniline 4g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC Rj=0.45(二氯甲烷： 甲醇 =7:1)  TLC Rj = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 778[M+H]十  ESI/MS: m/z 778[M+H] 十
实施例 99 Example 99
(21，38，41<，51 581，101 ,111 ,123，133，1411)-13-[(4-溴-2-氨基-嘧啶)-甲基]-11-[[3,4,6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8,10，12，14-六甲基 -1-氧-杂 -6- 替换页 （细则第 26条) 氮杂环十五垸 -15-酮 （结构式见下) (21, 38, 41 <, 51 5 81, 101, 111, 123, 133, 1411)-13-[(4-bromo-2-amino-pyrimidine)-methyl]-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 ,10,12,14-hexamethyl-1-oxo-hetero-6- replacement page (Article 26) Nitroheterocyclopentadecano-15-one (see below for structural formula)
Figure imgf000064_0001
Figure imgf000064_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-氨基 -5-溴 -嘧啶 4g" , 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-amino-5-bromo-pyrimidine 4g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 763[M+H]十  ESI/MS: m/z 763[M+H] 十
实施例 100 Example 100
(21^38,411,51 ,811,1(^,11R， 12S，13S，14R)-13-[(3,5-双-三氟甲基 -苯基氨基) -甲基 ]-11-[[3，4，6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10，12，14-六甲基 -1- 氧-杂 -6-氮杂环十五垸 -15-酮 （结构  (21^38,411,51,811,1(^,11R, 12S,13S,14R)-13-[(3,5-bis-trifluoromethyl-phenylamino)-methyl]-11-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 ,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (structure
Figure imgf000064_0002
Figure imgf000064_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3,5-双三氟甲基苯胺 4mL" , 其余同实施 例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "3,5-bistrifluoromethylaniline 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 818[M+H]  ESI/MS: m/z 818[M+H]
实施例 101 Example 101
(2R，3S，4R，5R，8R，10R,l lR，12S，13S，14R)-ll-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] - 2-乙基 -13-[(2,4-二硝基 -苯基氨基) -甲基 ]-3,4,10,13-四羟基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮 （结构式见  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-ll-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-13-[(2,4-dinitro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy-3,5 ,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000064_0003
Figure imgf000064_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2，4- 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2,4- intermediate to obtain 0.26 g of crude material to give the title compound.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
63 63
替换页 （细则第 26条) ESI/MS: m/z 772[M+H]+ Replacement page (Article 26) ESI/MS: m/z 772[M+H] +
实施例 102 Example 102
(2R，3S,4R,5R，8R,10R，l li 2S，13S,14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3，4，10,13-四羟基 -3，5,8,10,12,14-六甲基 -13-{ [(吗啉 -4-基-甲基) -氨基] -甲基 }1-氧- 杂 -6-氮杂环十五烷 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,l li 2S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{[(morpholine- 4-yl-methyl)-amino]-methyl}1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000065_0001
Figure imgf000065_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "N-甲氨基吗啉 4mL" , 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "t-butylamine 4.5 mL" in Example 14 was changed to use "N-methylaminomorpholine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲烷： 甲醇 =7:1)  TLC 3⁄4 = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 705[M+H]  ESI/MS: m/z 705 [M+H]
实施例 103 Example 103
(2R,3S,4R,5R，8R,10R,l lR,12S,13S，14R)-13-[(4-氨基 -吡啶 -3-基-氨基) -甲基 ]-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5,8，10,12，14-六甲基 -1-氧 -杂 -6-氮杂环十五烷 -15-酮 （结构式  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4-amino-pyridin-3-yl-amino)-methyl]-11-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 ,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (structural formula
Figure imgf000065_0002
Figure imgf000065_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3,4-二氨基吡啶 4g"， 其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3,4-diaminopyridine 4g", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC R产 0·45(二氯甲垸： 甲醇 =7:1)  TLC R production 0·45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 698[M+H]+ ESI/MS: m/z 698[M+H] +
实施例 104 Example 104
(21，38,41，51，81，101，111 ,128，138,1411)-13-[(2-氯-苄基氨基)-甲基]-11-[[3，4,6-三脱氧-3-(二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下）  (21, 38, 41, 51, 81, 101, 111, 128, 138, 1411)-13-[(2-chloro-benzylamino)-methyl]-11-[[3,4,6-three Deoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000065_0003
Figure imgf000065_0003
替换页 （细则第 26条) 将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2-氯苄胺 4mL"， 其余同实施例 14。 中间 获得 0.26g粗品， 最终得标题化合物。 Replacement page (Article 26) The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2-chlorobenzylamine 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 730[M+H]十  ESI/MS: m/z 730[M+H] 十
实施例 105 Example 105
(2R,3S,4R，5R，8R，10R，l lR,12S，13S，14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -13-[(2,4-二甲基 -苯基氨基) -甲基 ]-3，4，10，13-四羟基 -3，5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮 （结构式见  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D- Hexylpyranosyl]oxy]-2-ethyl-13-[(2,4-dimethyl-phenylamino)-methyl]-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000066_0001
Figure imgf000066_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2,4-二甲基苯胺 4mL"，其余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2,4-dimethylaniline 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC ¾=0.45(二氯甲垸： 甲醇 =7:1)  TLC 3⁄4=0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 710[M+H]+ ESI/MS: m/z 710[M+H] +
实施例 106 Example 106
(21，38，411，51，81 ,101，111，128，133,1411)-13-[(3-氯-苯基氨基)-甲基]-11-[[3,4，6-三脱氧-3-(二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12，14-六甲基 -1-氧-杂 -6-氮 杂环十五貌 -15-酮 （结构式见下） (21,38,411,51,81,101,111,128,133,1411)-13-[(3-chloro-phenylamino)-methyl]-11-[[3,4,6-three Deoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-ketone (see below for structural formula)
Figure imgf000066_0002
Figure imgf000066_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3-氯苯胺 4mL"， 其余同实施例 14。 中间 获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-chloroaniline 4 mL", and the rest was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 -7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol -7:1)
ESI/MS: m7z 716[M+H]+ ESI/MS: m7z 716[M+H] +
实施例 107 Example 107
(2R,3S，4R，5R，8R，10R,l lR，12S，13S,14R)-13-{[(5-氨基 -1，3，3-三甲基-环己基甲基) -氨基] -甲 基 }-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[(5-amino-1,3,3-trimethyl-cyclohexylmethyl)-amino] -Methyl}-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4 ,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
65 65
替换页 （细则第 26条)
Figure imgf000067_0001
Replacement page (Article 26)
Figure imgf000067_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3-甲氨基 -3,5,5-三甲基环己胺 4mL" ， 其 余同实施例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-methylamino-3,5,5-trimethylcyclohexylamine 4 mL", which was the same as in Example 14. 0.26 g of crude product was obtained in the middle to give the title compound.
TLC Rf=0.45(二氯甲烷： 甲醇 =7:1)  TLC Rf = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 759[M+H]+ ESI/MS: m/z 759[M+H] +
实施例 108 Example 108
(2R,3S，4R,5R，8R,10R，llR,12S，13S,14R)-13-((2,3-二氯 -6-硝基 -苄基氨基)甲基) -11-[[3，4，6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10,12，14-六甲基 -1- 氧-杂 -6-氮杂环十五焼 -15-酮 （结构  (2R,3S,4R,5R,8R,10R,llR,12S,13S,14R)-13-((2,3-Dichloro-6-nitro-benzylamino)methyl)-11-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 ,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (structure
Figure imgf000067_0002
Figure imgf000067_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "2，3- 例 14。 中间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "2,3-invention 14. In the middle, 0.26 g of crude product was obtained to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 810[M+H]十  ESI/MS: m/z 810[M+H]10
实施例 109 Example 109
(2R，3S,4R,5R，8R，10R,l lR,12S，13S，14R)-13-[(4-氯 -苯基氨基) -甲基] - 11-[[[3，4，6-三脱氧 -3- (二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5，8,10,12，14-六甲基小氧-杂 -6-氮 杂环十五垸 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4-chloro-phenylamino)-methyl] - 11-[[[3,4,6 -triptylo-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000067_0003
Figure imgf000067_0003
将实施例 14中的 "叔丁胺 4.5mL"改为使用 对氯苯胺 4g"， 其余同实施例 14。 中间 获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use p-chloroaniline 4g", and the rest was the same as in Example 14. In the middle, 0.26 g of crude product was obtained to give the title compound.
TLC Rf=0.45(二氯甲垸： 甲醇 =7:1)  TLC Rf = 0.45 (dichloroformamidine: methanol = 7:1)
ESI/MS: m/z 716[M+H]  ESI/MS: m/z 716[M+H]
66 66
替换页 （细则第 26条) (21，38，41，511,81，101，111，128，138，141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基—)-卩一-13'-^"吡 木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8，10，12,14-六甲基 -13- (喹啉 -6-基 -氨基甲基)小氧-杂 -6-氮杂 环十五烷 -15-酮 （结构式见下） Replacement page (Article 26) (21,38,41,511,81,101,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino-)-oxime--13'-^"pyroxy"oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- (quinoline- 6-yl-aminomethyl)oxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000068_0001
Figure imgf000068_0001
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "6-氨基喹啉 4g"， 其余同实施例 14。 中 间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "6-aminoquinoline 4g", and the rest was the same as in Example 14. In the middle, 0.26 g of crude product was obtained, which gave the title compound.
TLC ¾=0.45(二氯甲烷： 甲醇 =7:1)  TLC 3⁄4 = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 733[M+H]+ ESI/MS: m/z 733[M+H] +
实施例 1U Example 1U
(2尺，35,411,511，811，101 ,111，125，138，141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基) -0-己吡喃木糖基] 氧基] -2-乙基 -3，4，10，13-四羟基 -13-[(3- 基 -丙基氨基) -甲基 ]-3，5，8，10,12，14-六甲基小氧-杂 -6- 氮杂环十五烷 -15-酮 （结构式见下）  (2 feet, 35, 411, 511, 811, 101, 111, 125, 138, 141) -11-[[3,4,6-trideoxy-3-(dimethylamino)-0-hexyranidyl] Oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-yl-propylamino)-methyl]-3,5,8,10,12,14-six Methyl small oxygen-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000068_0002
Figure imgf000068_0002
将实施例 14中的 "叔丁胺 4.5mL"改为使用 "3-羟基丙胺 4mL"， 其余同实施例 14。 中 间获得 0.26g粗品， 最终得标题化合物。  The "tert-butylamine 4.5 mL" in Example 14 was changed to use "3-hydroxypropylamine 4 mL", and the rest was the same as in Example 14. In the middle, 0.26 g of crude product was obtained, which gave the title compound.
TLC Rf=0.45(二氯甲烷： 甲醇 =7:1)  TLC Rf = 0.45 (dichloromethane: methanol = 7:1)
ESI/MS: m/z 664[M+H]十  ESI/MS: m/z 664[M+H] 十
实顏 Real
(2R,3S，4R,5R,8R，10R,llR，12S,13S,14R)-ll-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8,10,12，14-六甲基 -13- (吗啉 -4-基-氨基甲基 )-1-氧-杂 -6-氮杂 环十五垸 ·15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,llR,12S,13S,14R)-ll-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexidyl Erlycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- (morpholin-4-yl -aminomethyl)-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000068_0003
Figure imgf000068_0003
将实施例 9中的 "2-羟基 -3-甲基-苄胺"改为使用 "4-氨基吗啉" ， 其余同实施例 9。 最 终得标题化合物 0.16g。 替换页 （细则第 26条) TLC ¾=0.44(二氯甲烷： 甲醇 =5:1) The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to "4-aminomorpholine", and the rest was the same as in Example 9. The title compound was finally obtained in an amount of 0.16 g. Replacement page (Article 26) TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z691[M+H]  ESI/MS: m/z691[M+H]
实施例 113 Example 113
(2Ι 38,4Ι,5Ι,8Ι,10ΙΜ1Ι 128,138,14ίΙ)-11-[[3,46-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3,4,1013-四羟基 -35,8,101214-六甲基 -13-[(2-甲基氨基 -乙基氨基) -甲基 ]小氧- 杂 -6-氮杂环十五烷 -15-酮 （结构式见 (2Ι38,4Ι,5Ι,8Ι,10ΙΜ1Ι128,138,14ίΙ)-11-[[3,46-Trideoxy-3-(dimethylamino)-β-D-hexyranosyl]oxy] - 2 - ethyl - 3, 4, 1013- -35,8,101214- tetrahydroxy-hexamethyl-13 - [(2-methylamino - ethylamino) - methyl] small oxo - oxa-6 Azacyclopentadecane-15-one (see structure formula)
Figure imgf000069_0001
Figure imgf000069_0001
将化合物 6 (0.176g, 0.2mmoL), 四丁基碘化铵 (0.7398g2.0mmoL)和 2-N-甲基氨基-乙胺盐 酸盐 (0.40g)在甲醇 (5mL)中的溶液在 50°C搅拌 2天。 浓缩， 将剩余物溶于水 (20mL)和乙酸乙 酯 (20mL)。 静置分层后， 水层用乙酸乙酯 (3x20mL)洗漆。 合并有机相， 萃取物用盐水 (40mL) 洗涤，用无水硫酸钠干燥，过滤，滤液真空浓缩。残余物硅胶色谱纯化，用甲醇：二氯甲烷 ： 氨 水 (4~6 93.5-95.6 0.4)洗脱， 得 0.09g标题化合物。  A solution of compound 6 (0.176 g, 0.2 mmoL), tetrabutylammonium iodide (0.7398 g 2.0 mmol) and 2-N-methylamino-ethylamine hydrochloride (0.40 g) in methanol (5 mL) Stir at 50 ° C for 2 days. Concentrate and dissolve the residue in water (20 mL) and ethyl acetate (20 mL). After standing to separate the layers, the aqueous layer was washed with ethyl acetate (3×20 mL). The combined organic layers were washed with EtOAc EtOAc. The residue was purified by silica gel chromatography eluting elut elut elut elut elut elut elut
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z663[M+H]  ESI/MS: m/z663[M+H]
实施例 114 Example 114
(2R,3S,4R5R8R10R11R,12S13S14R)-13-环庚基氨基甲基 1-11-[[3,4,6-三脱氧 -3- (二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环 十五垸 -15-酮 （结构式见下）  (2R,3S,4R5R8R10R11R,12S13S14R)-13-Cycloheptylaminomethyl 1-1-1-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-hexyranium Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-6-azacyclocycle Fifteen 垸-15-ketone (see below for structural formula)
Figure imgf000069_0002
Figure imgf000069_0002
将实施例 9中的 "2-羟基 -3-甲基-苄胺"改为使用 "环庚胺"， 其余同实施例 9。 最终得 标题化合物 0.14g  The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to use "cycloheptylamine", and the remainder was the same as in Example 9. The title compound was finally obtained.
TLC R尸 0.44(二氯甲垸： 甲醇 =5:1)  TLC R corpse 0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z702[M+H]  ESI/MS: m/z702[M+H]
实施例 115 Example 115
4-{(2R,3S4R,5R,8R,10R,llR,12S,13S,14R)-ll-[[346-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖 基]氧基] -2-乙基 -3,4,10,13-四羟基 -35,810,1214-六甲基小氧 -15-酮-杂 -6-氮杂环十五垸 -13-基- 甲基] -氨基 } -酞腈（结构式见下） 4-{(2R,3S4R,5R,8R,10R,llR,12S,13S,14R)-ll-[[346-Trideoxy-3-(dimethylamino)-β-D-hexyryl xylose Ethyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-35,810,1214-hexamethyloxyxan-15-one-hetero-6-azacyclopentadepin-13-yl - methyl]-amino}-phthalonitrile (see below for structural formula)
替换页 （细则第 26条)
Figure imgf000070_0001
Replacement page (Article 26)
Figure imgf000070_0001
将实施例 Ί中的"环丙胺(2.43mL，2.00g，35mmoL)"改为使用 "4-氨基邻苯二甲腈 (2.43g)"， 其余同实施例 7。 最终得标题化合物 0.20g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in the Example was changed to "4-aminophthalonitrile (2.43 g)", and the rest was the same as in Example 7. The title compound was finally obtained to be 0.20 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 732[M+H]十  ESI/MS: m/z 732[M+H] 十
实施例 116 Example 116
(21 ,33，411，51 ,81，101 ,1111,123，133，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-3-0-己吡喃木糖基] 氧基] -2-乙基 -13-{ [(呋喃 -2-基-甲基) -氨基] -甲基 }-3,4，10,13-四羟基 -3,5，8,10,12,14-六甲基 -1-氧- 杂 -6-氮杂环十五垸 -15-酮 （结构式见  (21,33,411,51,81,101,1111,123,133,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexidyl Isokilyl]oxy]-2-ethyl-13-{[(furan-2-yl-methyl)-amino]-methyl}-3,4,10,13-tetrahydroxy-3,5 ,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000070_0002
Figure imgf000070_0002
将实施例 9中的 "2-羟基 -3-甲基-苄胺"改为使用 "2-甲氨呋喃"， 其余同实施例 9。 最 终得标题化合物 0.13g。  The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to "2-methylammonium", and the rest was the same as in Example 9. The title compound was finally obtained in an amount of 0.13 g.
TLC Rj=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rj = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 686[M+H]+ ESI/MS: m/z 686[M+H] +
实施例 117 Example 117
(21，38,411，51，8¾101 ,1111,128，138，1411)-11-[[3,4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -13-[(3-甲氧基-苯氨基) -甲基 ]-3,5，8，10，12，14-六甲基 -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  (21,38,411,51,83⁄4101,1111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-indole-0-hexyranose ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-methoxy-phenylamino)-methyl]-3,5,8,10,12,14 -hexamethyl-1-oxo-6-nitrozacyclopentadecane-15-one (see below for structural formula)
Figure imgf000070_0003
Figure imgf000070_0003
将实施例 7中的 "环丙胺 (2.43mL,2.00g,35mmoL)"改为使用 "3-甲氧基 -苯胺 (2.43mL)"， 其余同实施例 7。 最终得标题化合物 0.17g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to "3-methoxy-aniline (2.43 mL)", and the rest was the same as in Example 7. The title compound was finally obtained in 0.17 g.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 712[M+H] 替换页 （细则第 26条) 实施例 118 ESI/MS: m/z 712[M+H] replacement page (Article 26) Example 118
(21，38, ，511,81，101 ,1111,128，138，14 )-13-[(3-溴-苯基氨基)-甲基]-1 [[3,4，6-三脱氧-3-(二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5,8,10，12，14-六甲基小氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下）  (21,38, ,511,81,101,1111,128,138,14 )-13-[(3-bromo-phenylamino)-methyl]-1 [[3,4,6-trideoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000071_0001
Figure imgf000071_0001
将实施例 7中的 "环丙胺 (2.43mL,2.00g,35mmoL)"改为使用 "3-溴 -苯胺 (2.43g)"， 其余 同实施例 7。 最终得标题化合物 0.16g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "3-bromo-aniline (2.43 g)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.16 g.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 760[M+H]+ ESI/MS: m/z 760[M+H] +
实施例 119 Example 119
(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12,14-六甲基 -13-[(N-甲基-苯基-氨基) -甲基 ]-1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(N-A -Phenyl-amino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000071_0002
Figure imgf000071_0002
将实施例 9中的 "2-羟基 -3-甲基-苄胺"改为使用 "N-甲基苯胺"， 其余同实施例 9。 最 终得标题化合物 0.16g。  The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to use "N-methylaniline", and the rest was the same as in Example 9. The title compound was finally obtained in an amount of 0.16 g.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 696[M+H]十  ESI/MS: m/z 696[M+H] 十
实施例 120 Example 120
(2R,3S，4R，5R，8R，10R,l lR,12S,13S,14R)-13-[(2-氨基 -1-甲基 -乙基氨基) -甲基 ]- 11-[[3，4,6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10,12,14-六甲基 -1- 氧-杂 -6-氮杂环十五烷 -15-酮 （结构式见下） (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-amino-1-methyl-ethylamino)-methyl]- 11-[[3 ,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
70 70
替换页 （细则第 26条)
Figure imgf000072_0001
Replacement page (Article 26)
Figure imgf000072_0001
将实施例 7中的 "环丙胺 (2.43mL，2.00g,35mmoL)"改为使用 "2-氨基 -1-甲基 -乙胺 (2.43 mL)" ， 其余同实施例 7。 最终得标题化合物 0.15g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to "2-amino-1-methyl-ethylamine (2.43 mL)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.15 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 663[M+H]+ ESI/MS: m/z 663[M+H] +
实施例 Example
(21 ,38，411，51，81，1011，111，128，138,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-3-0-己吡喃木糖基] 氧基] -2-乙基 -13-[(4-乙块基 -2H-吡唑 -3-基-氨基) -甲基 ]-3,4,10,13-四羟基 -3，5,8,10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五院 -15-酮 （  (21,38,411,51,81,1011,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexpyran Glycosyl]oxy]-2-ethyl-13-[(4-ethylidyl-2H-pyrazol-3-yl-amino)-methyl]-3,4,10,13-tetrahydroxy-3 ,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azetidine fifteenth hospital-15-ketone (
Figure imgf000072_0002
Figure imgf000072_0002
将实施例 9中的 "2mL 2-羟基 -3-甲基-苄胺"改为使用 "2.0g 3-氨基 4-乙炔基 -2H-吡唑"， 并且将异丙醇用量由 5mL改为 25.0mL， 其余同实施例 9。 最终得标题化合物 0.1 lg。  Change "2mL 2-hydroxy-3-methyl-benzylamine" in Example 9 to use "2.0g 3-amino-4-ethynyl-2H-pyrazole", and change the amount of isopropanol from 5mL to 5mL. 25.0 mL, the rest was the same as in Example 9. The title compound was finally obtained as 0.1 lg.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 696[M+H]十  ESI/MS: m/z 696[M+H] 十
实施例 122 Example 122
(2¾38，41 ,51 ,811,10 ,1111，128,138，141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基 ]-2-乙基 -13-[(4-乙基 -6-甲基 -[1，3，5]三氮唑 -2-基 -氨基) -甲基 ]-3，4,10，13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂 式见下）  (23⁄438,41,51,811,10,1111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyranidyl ]oxy]-2-ethyl-13-[(4-ethyl-6-methyl-[1,3,5]triazol-2-yl-amino)-methyl]-3,4, 10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-aza is as shown below)
Figure imgf000072_0003
Figure imgf000072_0003
将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "2-氨基 -4-乙基 -6-甲基 -[1,3,5] 三氮唑"， 其余同实施例 121。 最终得标题化合物 0.12g。 替换页 （细则第 26条) TLC Rf=0.44(二氯甲垸： 甲醇 =5:1) The "3-amino-4-ethynyl-2H-pyrazole" in Example 121 was changed to use "2-amino-4-ethyl-6-methyl-[1,3,5]triazole", The rest are the same as in embodiment 121. The title compound was finally obtained in an amount of 0.12 g. Replacement page (Article 26) TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 727 [M+H]十  ESI/MS: m/z 727 [M+H] 十
实施例 123 Example 123
(21，38，41，51，81 ,101，111，128,138，141 )-13-[(4，6-二羟基-嘧啶-2-基-氨基)-甲基]-11-[[3，4，6-三 脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8,10,12，14-六甲基 -1-氧-杂 氮杂环十五焼 -15-酮 （结构  (21, 38, 41, 51, 81, 101, 111, 128, 138, 141)-13-[(4,6-dihydroxy-pyrimidin-2-yl-amino)-methyl]-11-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 , 8,10,12,14-hexamethyl-1-oxo-heterozacyclopentadecane-15-one (structure
Figure imgf000073_0001
Figure imgf000073_0001
将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "4,6-二羟基 -2-氨基嘧啶"， 其 余同实施例 121。 最终得标题化合物 0.12g。  The "3-amino-4-ethynyl- 2H-pyrazole" in Example 121 was changed to use "4,6-dihydroxy-2-aminopyrimidine", which was the same as Example 121. The title compound was finally obtained in an amount of 0.12 g.
Rf=0.44(二氯甲垸： 甲醇 =5:1)  Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 716 [M+H]+ ESI/MS: m/z 716 [M+H] +
实施例 124 Example 124
(2R,3S,4R,5R,8R, 10R， 11 R, 12S， 13 S， 14R)- 13 -癸垸基氨基甲基 - 11 -[[3,4,6-三脱氧 -3- (二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环 十五烧 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R, 10R, 11 R, 12S, 13 S, 14R)- 13 -decylaminomethyl- 11 -[[3,4,6-trideoxy-3- (two Methylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexa Base-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000073_0002
Figure imgf000073_0002
将实施例 7中的 "环丙胺(2.431¾1^，2.0(^，3511^101 "改为使用 "癸胺 (2.43mL)"， 其余同 实施例 7。 最终得标题化合物 0.13g。 The "cyclopropylamine (2.431 3⁄4 1^, 2.0 (^, 351 1 ^ 101" was changed to use "decylamine (2.43 mL)" in Example 7 and the rest was the same as in Example 7. The title compound was obtained.
TLC R产 0.44(二氯甲烷： 甲醇 =5:1)  TLC R yield 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 746 [M+H]  ESI/MS: m/z 746 [M+H]
实施例 125 Example 125
3-{(211，33,41 ,511，81 ,101，111 ,125,138,1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基) -0-己吡喃木糖 基]氧基 ]-2-乙基 -3,4，10，13-四羟基 -3,5，8，10，12，14-六甲基 -15-酮 -1-氧-杂 -6-氮杂环十五烷 -13-基- 甲基] -氨基 }-正丁酸 （结构式见下）  3-{(211,33,41 ,511,81 ,101,111 ,125,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one-1-oxo-hetero- 6-azacyclopentadecane-13-yl-methyl]-amino}-n-butyric acid (see below for structural formula)
Figure imgf000073_0003
Figure imgf000073_0003
替换页 （细则第 26条) 将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "3-氨基丁酸"， 其余同实施例 121。 最终得标题化合物 0.14g。 Replacement page (Article 26) The "3-amino-4-ethynyl-2H-pyrazole" in Example 121 was changed to use "3-aminobutyric acid", and the rest was the same as in Example 121. The title compound was finally obtained in an amount of 0.14 g.
TLC R尸 0.44(二氯甲烷： 甲醇 =5:1)  TLC R corpse 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 692 [M+H]  ESI/MS: m/z 692 [M+H]
实施例 126 Example 126
(2R，3S,4R，5R，8R，10R，l lR，12S，13S,14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3,4，10，13-四羟基 -13-[(1-羟基甲基 -丙基氨基) -甲基 ]-3,5,8，10，12,14-六甲基 -1-氧- 杂 -6-氮杂环十五垸 -15-酮 （结构式见  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(1-hydroxymethyl-propylamino)-methyl]-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000074_0001
Figure imgf000074_0001
将实施例 7中的"环丙胺 (2.43mL，2.00g，35mmoL)"改为使用" 1-羟基甲基 -丙胺 (2.43mL)"， 其余同实施例 7。 最终得标题化合物 0.15g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "1-hydroxymethyl-propylamine (2.43 mL)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.15 g.
TLC ¾=0.42(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.42 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 678 [M+H]十  ESI/MS: m/z 678 [M+H] 十
实施例 127 Example 127
(2R,3S，4R,5R，8R,10I lR,12S，13S,14R)-l l-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10，12，14-六甲基 -13-[(2-苯基 -丙基氨基) -甲基 ]1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下） (2R,3S,4R,5R,8R,10I lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexidyl Erlycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(2-phenyl- Propylamino)-methyl]1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000074_0002
Figure imgf000074_0002
将实施例 7中的 "环丙胺 (2.43mL,2.00g,35mmoL)"改为使用 "2-苯基 -丙胺 (2.43mL)"， 其余同实施例 7。 最终得标题化合物 0.13g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "2-phenyl-propylamine (2.43 mL)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.13 g.
TLC ¾=0.41(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4=0.41 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 724[M+H]+ ESI/MS: m/z 724[M+H] +
实施例 128 Example 128
磺酸单 -2-{(2R,3S,4R,5R,8R，10R,l lR,12S，13S，14R)-l l-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12,14-六甲基 -1-氧 -15-酮-杂 -6-氮杂环十五烷 -13-基-甲基] -氨基 }-乙基酯 （结构式见下） Sulfonic acid mono-2-{(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-trideoxy-3-(dimethyl Amino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl- 1-oxo-15-keto-hetero-6-azetidine pentadecyl-13-yl-methyl]-amino}-ethyl ester (see below for structural formula)
73 73
替换页 （细则第 26条)
Figure imgf000075_0001
Replacement page (Article 26)
Figure imgf000075_0001
将实施例 7中的 "环丙胺 (2.43mL,2.00g，35mmoL)"改为使用 "磺酸乙胺酯 (2.43g)"， 其 余同实施例 7。 最终得标题化合物 0.16g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "ethylamine sulfonate (2.43 g)", which was the same as in Example 7. The title compound was finally obtained in an amount of 0.16 g.
TLC Rf0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 730[M+H]+ ESI/MS: m/z 730[M+H] +
实施例 129 Example 129
(2R,3S,4R,5R，8R，10R,l lR,12S，13S,14R)-13-[(3,4-二氟 -苯基氨基) -基] -11-[[3,4,6-三脱氧 -3- (二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,4-difluoro-phenylamino)-yl]-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 ,10,12,14-hexamethyl-1-oxo-6-nitrozacyclopentadecane-15-one (see below for structural formula)
Figure imgf000075_0002
Figure imgf000075_0002
将实施例 7中的 "环丙胺 (2.43mL，2.00g,35mmoL)"改为使用 "3,4-二氟-苯胺(2.438)"， 其余同实施例 7。 最终得标题化合物 0.18g。 The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "3,4-difluoro-aniline (2.43 8 )", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.18 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 718[M+H]+ ESI/MS: m/z 718[M+H] +
实施例 130 Example 130
(2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(3,5-二氟 -苄基氨基） -甲基 ]-11 -[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5，8，10，12,14-六甲基 -1-氧 -杂 -6-氮杂环十五烷 -15-酮 （结构式见  (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(3,5-difluoro-benzylamino)-methyl]-11 -[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000075_0003
Figure imgf000075_0003
将实施例 121 中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "3，5-二氟-苄氨"， 且将异丙 醇的用量由 25mL改为 10mL, 其余同实施例 121。 最终得标题化合物 0.16g。  The "3-amino-4-ethynyl-2H-pyrazole" in Example 121 was changed to use "3,5-difluoro-benzylamine", and the amount of isopropanol was changed from 25 mL to 10 mL. Example 121. The title compound was finally obtained in an amount of 0.16 g.
TLC R尸 0.44(二氯甲垸： 甲醇 =5:1)  TLC R corpse 0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 732[M+H]十  ESI/MS: m/z 732[M+H] 十
74 74
替换页 （细则第 26条) 实施例 131 Replacement page (Article 26) Example 131
(21，38，41，51 581，101 ,111，128，138,141 )-13-[(4，4-双甲氧基-正丁基氨基)-甲基]-11-[[3,4,6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10，13-四羟基 -3,5,8，10，12,14-六甲基小 氧-杂 -6-氮杂环十五垸 -15-酮 （结构 (21,38,41,51 5 81,101,111,128,138,141 )-13-[(4,4-bismethoxy-n-butylamino)-methyl]-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (structure
Figure imgf000076_0001
Figure imgf000076_0001
将实施例 9中的 "2-羟基 -3-甲基-苄胺"改为使用 "4,4-双甲氧基-正丁氨"， 其余同实施 例 9。 最终得标题化合物 0.12g。  The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to use "4,4-bismethoxy-n-butylamine", and the rest was the same as in Example 9. The title compound was finally obtained in an amount of 0.12 g.
TLC Ri=0.44(二氯甲垸： 甲醇 =5:1)  TLC Ri=0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 722[M+H]十  ESI/MS: m/z 722[M+H] 十
实施例 132 Example 132
(2R,3S,4 ,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,4-二氯 -苄基氨基） -甲基 ]-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8,10,12,14-六甲基 -1-氧 -杂 -6-氮杂环十五垸 -15-酮 （结构式见  (2R,3S,4,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,4-Dichloro-benzylamino)-methyl]-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000076_0002
Figure imgf000076_0002
将实施例 9中的 "2mL 2-羟基 -3-甲基-苄胺"改为使用 "2.0g 3,4-二氯-苄氨"， 其余同实 施例 9。 最终得标题化合物 0.1 lg。  The "2 mL of 2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to use "2.0 g of 3,4-dichloro-benzylamine", and the rest was the same as Example 9. The title compound was finally obtained as 0.1 lg.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 764[M+H]+ ESI/MS: m/z 764[M+H] +
实施例 133 Example 133
(21，38，411，51，81，101，1111，128，138,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基)-3-0-己吡喃木糖基] 氧基] -2-乙基 -3,4，10，13-四羟基 -13-[(2-甲氧基 -乙基氨基) -甲基 ]-3，5,8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮 （结构式见 (21,38,411,51,81,101,1111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexidyl Isokilyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(2-methoxy-ethylamino)-methyl]-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000076_0003
Figure imgf000076_0003
替换页 （细则第 26条) 将实施例 9中的 "2mL 2-羟基 -3-甲基-苄胺"改为使用 "5mL 2-甲氧基-乙氨" ， 其余同 实施例 9。 最终得标题化合物 0.10g Replacement page (Article 26) The "2 mL of 2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to use "5 mL of 2-methoxy-ethylamine", and the rest was the same as in Example 9. The title compound was finally obtained 0.10g
TLC R产 0.44(二氯甲垸： 甲醇 =5:1)  TLC R yield 0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 664[M+H]+ ESI/MS: m/z 664[M+H] +
实施例 134 Example 134
(2R,3S4R,5R8R10RllR,12S13S,14R)-13-[(4-二乙基氨基小甲基 -丁基氨基) -甲基] - 11 -[3 ,4,6- 三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基）]-2-氧 -2-乙基 -3,41013-四羟基 -358,1012,14-六甲 基 -1-氧-杂 -6-氮杂环十五院 -15-酮  (2R,3S4R,5R8R10RllR,12S13S,14R)-13-[(4-Diethylaminosodiummethyl-butylamino)-methyl] - 11 -[3 ,4,6-trideoxy-3- ( Dimethylamino)-β-D-hexylpyranosyl)]-2-oxo-2-ethyl-3,41013-tetrahydroxy-358,1012,14-hexamethyl-1-oxo-hetero -6-nitrogen heterocyclic fifteenth hospital-15-ketone
Figure imgf000077_0001
Figure imgf000077_0001
将实施例 9 中的 "2-羟基 -3-甲基-苄胺"改为使用 "4-二乙基氨基 -1-甲基-丁氨"， 其余 同实施例 9。 最终得标题化合物 0.15g  The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to use "4-diethylamino-1-methyl-butylamine", and the rest was the same as in Example 9. The title compound was finally obtained. 0.15g
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z747[M+H]  ESI/MS: m/z747[M+H]
实施例 135 Example 135
(2R,3S,4R5R,8R10RllI 2S13S,14R)-13-[(3-环己基氨基 -丙基氨基) -甲基] - 11-[[[3,4,6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -358,10,1214-六甲基小 氧-杂 -6-氮杂环十五垸 -15-酮 （结 (2R,3S,4R5R,8R10RllI 2S13S,14R)-13-[(3-Cyclohexylamino-propylamino)-methyl] -11-[[[3,4,6-trideoxy-3- (II Methylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-358,10,1214-hexamethyloxy-hetero- 6-azacyclopentadecane-15-one (knot)
Figure imgf000077_0002
Figure imgf000077_0002
将实施例 7中的 "环丙胺 (2.43mL,2.00g35mmoL)"改为使用 "3-环己基氨基 -丙胺 (2.43 mL)"， 其余同实施例 7。 最终得标题化合物 0.18g  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "3-cyclohexylamino-propylamine (2.43 mL)", and the rest was the same as in Example 7. The title compound was finally obtained 0.18g
TLC R尸 0.44(二氯甲垸： 甲醇 =5:1)  TLC R corpse 0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z746[M+H]  ESI/MS: m/z746[M+H]
实施例 136 Example 136
(2R,3S,4R,5R,8R,10RllR12S,13S,14R)-13-((3,4-二氯苄基氨基)甲基)- 11-[[3,46-三脱氧 -3- (二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -358101214-六甲基小氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10RllR12S,13S,14R)-13-((3,4-Dichlorobenzylamino)methyl)- 11-[[3,46-trideoxy-3- ( Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-358101214-hexamethyloxy-hetero-6-nitrogen Heterocyclic fifteen-15-one (see below for structural formula)
76 76
替换页 （细则第 26条)
Figure imgf000078_0001
Replacement page (Article 26)
Figure imgf000078_0001
将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "3,4-二氯苄氨"， 其余同实施 例 121。 最终得标题化合物 0.14g。  The "3-amino-4-ethynyl- 2H-pyrazole" in Example 121 was changed to use "3,4-dichlorobenzylamine", and the remainder was the same as in Example 121. The title compound was finally obtained in an amount of 0.14 g.
TLC R =0.44(二氯甲垸： 甲醇 =5:1)  TLC R = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 765[M+H]十  ESI/MS: m/z 765[M+H] 十
实施例 137 Example 137
(211,38,4 511,81 ,101 ,1111,128，138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-3-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12,14-六甲基 -13-[(1-甲基-正丁基氨基) -甲基 ]小氧-杂 -6-氮杂环十五垸 -15-酮 （结构式见下）  (211,38,4 511,81 ,101 ,1111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyryl xylose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(1-methyl-n-butyl) Amino)-methyl]sodiumoxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000078_0002
Figure imgf000078_0002
将实施例 7中的 "环丙胺 (2.43mL，2.00g，35mmoL)"改为使用 " 1-甲基-正丁胺 (2.43mL)" ， 其余同实施例 7。 最终得标题化合物 0.18g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "1-methyl-n-butylamine (2.43 mL)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.18 g.
TLC R尸 0.44(二氯甲烷： 甲醇 =5:1)  TLC R corpse 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 676[M+H]十  ESI/MS: m/z 676[M+H] 十
实施例 138 Example 138
(21^33,411,51 ,81 ，101 ,1111，128，138，1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -13-[(4-羟基 -3-甲氧基 -苄基氨基) -甲基 ]3，5，8，10,12，14-六甲基小 氧-杂 -6-氮杂环十五垸 -15-酮 （结构  (21^33,411,51,81,101,1111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(4-hydroxy-3-methoxy-benzylamino)-methyl]3,5,8 ,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (structure
Figure imgf000078_0003
Figure imgf000078_0003
将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "4-羟基 -3-甲氧基-苄氨"， 其 余同实施例 121。 最终得标题化合物 0.24g。  The "3-amino-4-ethynyl- 2H-pyrazole" in Example 121 was changed to use "4-hydroxy-3-methoxy-benzylamine", which was the same as Example 121. The title compound was finally obtained in an amount of 0.24 g.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ES画 S: m/z 742[M+H]十 ES painting S : m/z 742[M+H] ten
实施例 139 替换页 （细则第 26条) (21，38,411，51 ,81 ,101，111 ,123,133,1411)-11-[[3，4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -13-[(2-吡啶 -3-基 -乙基氨基) -甲基 ]小氧- 杂 -6-氮杂环十五垸 -15-酮 （结构式见 Example 139 Replacement Page (Rule 26) (21,38,411,51,81,101,111,123,133,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyranidyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(2-pyridin-3-yl-ethyl) Base amino)-methyl]sodiumoxy-hetero-6-nitroheicyclopentadecane-15-one (see structure formula)
Figure imgf000079_0001
Figure imgf000079_0001
将实施例 7中的 "环丙胺 (2.43mL,2.00g,35mmoL)"改为使用 "2-吡啶基 -乙胺 (2.43mL)" , 其余同实施例 7。 最终得标题化合物 0.18g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "2-pyridyl-ethylamine (2.43 mL)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.18 g.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 711[M+H]十  ESI/MS: m/z 711[M+H] ten
实施例 140 Example 140
(21，38,4 51 ,81，101^111 ,125,138,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8，10，12,14-六甲基 -13-[(3-三氟甲基 -苄基氨基) -甲基 ]小氧- 杂 -6-氮杂环十五垸 -15-酮 （结构式见下）  (21,38,4 51 ,81,101^111 ,125,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyryl xylose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(3-trifluoromethyl-benzyl) Base amino)-methyl]sodiumoxy-hetero-6-nitroheicyclopentadecane-15-one (see below for structural formula)
Figure imgf000079_0002
Figure imgf000079_0002
将实施例 7中的"环丙胺 (2.43mL,2.00g,35mmoL)"改为使用" 3-三氟甲基 -苄胺 (2.43mL)"， 其佘同实施例 7。 最终得标题化合物 0.14g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to "3-trifluoromethyl-benzylamine (2.43 mL)", which is the same as in Example 7. The title compound was finally obtained in an amount of 0.14 g.
TLC ¾=0.44(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 764[M+H]+ ESI/MS: m/z 764[M+H] +
实施例 141 Example 141
(21 ,33，41，511,81，101，111 ,123,138,141 -13-[(2-氨基-苄基氨基)-甲基]-11-[[3，4，6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10,13-四羟基 -3，5,8，10,12，14-六甲基 -1-氧-杂 -6- 氮杂环十五浣 -15-酮  (21,33,41,511,81,101,111,123,138,141 -13-[(2-amino-benzylamino)-methyl]-11-[[3,4,6-trideoxy-3-( Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-six Methyl-1-oxo-hetero-6-azacyclopentadecane-15-one
Figure imgf000079_0003
Figure imgf000079_0003
将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "2-氨基-苄氨" ， 其余同实施 例 121。 最终得标题化合物 0.22g。  The "3-amino-4-ethynyl- 2H-pyrazole" in Example 121 was changed to use "2-amino-benzylamine", and the remainder was the same as in Example 121. The title compound was finally obtained in an amount of 0.22 g.
替换页 （细则第 26条) TLC Rf=0.44(二氯甲烷： 甲醇 =5:1) Replacement page (Article 26) TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 711[M+H]+ ESI/MS: m/z 711[M+H] +
实施例 142 Example 142
(21，38，41 ,511,81 ,101 ,111 5128，138,141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基) -0-己吡喃木糖基] 氧基] -2-乙基 -3，4,10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-{[(5-甲基 -吡唑 -2-基-甲基) -氨基] -甲 基 }小氧-杂 -6-氮杂环十五浣 -15-酮 (21,38,41,511,81,101,111 5 128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranidyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{[(5-methyl-pyrazole- 2-yl-methyl)-amino]-methyl}sodiumoxy-hetero-6-azacyclopentadecane-15-one
Figure imgf000080_0001
Figure imgf000080_0001
将实施例 7中的"环丙胺 (2.43mL，2.00g,35mmoL)"改为使用" 2-甲基 -吡唑 -5-甲胺 (2.43g)"， 其余同实施例 7。 最终得标题化合物 0.26g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "2-methyl-pyrazole-5-methylamine (2.43 g)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.26 g.
Ri=0.44(二氯甲烷： 甲醇 =5:1)  Ri = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 712[M+H]十  ESI/MS: m/z 712[M+H] 十
实施例 143 Example 143
(21 ,38，411，51 ,8 101 ,111，128,138，141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基)-3-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -13-[(3-甲氧基 -丙基氨基) -甲基 ]-3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五'垸 -15-酮  (21,38,411,51,8 101,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyryl xylose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-methoxy-propylamino)-methyl]-3,5,8,10,12 ,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15'-15-one
Figure imgf000080_0002
Figure imgf000080_0002
将实施例 9中的 "2-羟基 -3-甲基-苄胺"改为使用 "3-甲氧基-丙胺" ， 其余同实施例 9。 最终得标题化合物 0.24g。  The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to use "3-methoxy-propylamine", and the rest was the same as in Example 9. The title compound was finally obtained in an amount of 0.24 g.
TLC ¾=0.44(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 678[M+H]  ESI/MS: m/z 678[M+H]
实施例 144 Example 144
(2R，3S,4R，5R,8R，10R，11R，12S,13S,14R)-13- [(环己基-甲基-氨基) -甲基 ]-11-[[3,4，6-三脱氧 -3- (二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10,12,14-六甲基小氧-杂 -6- 氮杂环十五垸 -15-酮  (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13- [(cyclohexyl-methyl-amino)-methyl]-11-[[3,4,6-three Deoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one
79 79
替换页 （细则第 26条)
Figure imgf000081_0001
Replacement page (Article 26)
Figure imgf000081_0001
将实施例 9中的 "2-羟基 -3-甲基-苄胺"改为使用 "环己基-甲胺"， 其余同实施例 9。 最 终得标题化合物 0.14g。  The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to use "cyclohexyl-methylamine", and the rest was the same as in Example 9. The title compound was finally obtained in an amount of 0.14 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 702[M+H]+ ESI/MS: m/z 702[M+H] +
实施例 145 Example 145
(2 ，38，411，51，81 ,101，1111,128，138，1411)-11-[[3,4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-[(1,2，2-三甲基 -丙基氨基) -甲基 ]小氧- 杂 -6-氮杂环十五烷 -15-酮  (2,38,411,51,81,101,1111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexidyl Erlycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(1,2,2 -trimethyl-propylamino)-methyl]sodiumoxy-hetero-6-azacyclopentadecane-15-one
Figure imgf000081_0002
Figure imgf000081_0002
将实施例 7中的"环丙胺 (2.43mL，2.00g，35mmoL)"改为使用" 3，3-二甲基 -2-丁胺 (2.43mL)"， 其余同实施例 7。 最终得标题化合物 0.22g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "3,3-dimethyl-2-butylamine (2.43 mL)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.22 g.
TLC Ri=0.44(二氯甲垸： 甲醇 =5:1)  TLC Ri=0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 690[M+H]十  ESI/MS: m/z 690[M+H] 十
实施例 1 Example 1
(21，38，411，51 ,81，101 ,111 ,128,138，141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基) -0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟 -3，5,8，10，12，14-六甲基 -13- (哌啶 -4-基-氨基甲基 )小氧-杂 -6-氮杂环 十五烷 -15-酮  (21,38,411,51,81,101,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranidyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(piperidin-4-yl-aminomethyl) Small oxygen-hetero-6-azacyclopentadecane-15-one
Figure imgf000081_0003
Figure imgf000081_0003
将实施例 7中的 "环丙胺 (2.43mL,2.00g,35mmoL)"改为使用 "4-氨基 -哌啶 (2.43g)"， 其 余同实施例 7。 最终得标题化合物 0.13g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "4-amino-piperidine (2.43 g)", which was the same as in Example 7. The title compound was finally obtained in an amount of 0.13 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 689[M+H]  ESI/MS: m/z 689[M+H]
实施例 147 替换页 （细则第 26条) (2R，3S,4R，5R,8R，10R，l lR,12S，13S，14R)-ll-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -13-[(2-氟 -苯基氨基) -甲基 ]-3，4，10,13-四羟基 -3，5，8,10，12,14-六甲基小氧-杂 -6-氮 杂环十五垸 -15-酮 Example 147 Replacement Page (Rule 26) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-ll-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-13-[(2-fluoro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy-3,5,8,10 ,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one
Figure imgf000082_0001
Figure imgf000082_0001
将实施例 7中的 "环丙胺 (2.43mL，2.00g,35mmoL)"改为使用 "2-氟 -苯胺 (2.43mL)"， 其 余同实施例 7。 最终得标题化合物 0.36g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "2-fluoro-aniline (2.43 mL)", which was the same as in Example 7. The title compound was finally obtained in an amount of 0.36 g.
TLC ¾=0.14(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.14 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 700[M+H]+ ESI/MS: m/z 700[M+H] +
实施例 148 Example 148
(211,33,41，51 ,81，101 ,1111,128,138,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -13-[(4-氟 -苯基氨基) -甲基 ]-3,4,10,13-四羟基 -3,5，8，10,12，14-六甲基小氧-杂 -6-氮 杂环十五烷 -15-酮  (211, 33, 41, 51, 81, 101, 1111, 128, 138, 141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyrranoxyl ]oxy]-2-ethyl-13-[(4-fluoro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyloxy-hetero-6-azacyclopentadecane-15-one
Figure imgf000082_0002
Figure imgf000082_0002
将实施例 7中的 "环丙胺 (2.43mL,2.00g,35mmoL)"改为使用 "4-氟 -苯胺 (2.43mL)" , 其 余同实施例 7。 最终得标题化合物 0.17g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "4-fluoro-aniline (2.43 mL)", which was the same as in Example 7. The title compound was finally obtained in 0.17 g.
TLC R产 0.24(二氯甲垸： 甲醇 =5:1)  TLC R yield 0.24 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 700[M+H]+ ESI/MS: m/z 700[M+H] +
实施例 149 Example 149
(21 ,38，411,511，81，101 ,111 ,123,133,141 )-13-[(4-二乙基氨基-苯基基)-甲基]-1-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12，14-六甲基 -1-氧 -杂 -6-氮杂环十五垸 -15-酮  (21,38,411,511,81,101,111,123,133,141)-13-[(4-Diethylamino-phenyl)-methyl]-1-[[3,4,6-trideoxy-3 - (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 -hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
Figure imgf000082_0003
Figure imgf000082_0003
将实施例 9中的 "2-羟基 -3-甲基-苄胺"改为使用 "4-二乙基氨基-苯氨"， 并且异丙醇用 量由 5mL改为 10mL, 其余同实施例 9。 最终得标题化合物 0.26g。  The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to use "4-diethylamino-phenylamine", and the amount of isopropanol was changed from 5 mL to 10 mL, and the rest was the same as in Example 9. . The title compound was finally obtained in an amount of 0.26 g.
81  81
替换页 （细则第 26条) TLC Rf=0.44(二氯甲垸： 甲醇 =5:1) Replacement page (Article 26) TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 753[M+H]十  ESI/MS: m/z 753[M+H] 十
实施例 ¾50 Example 3⁄450
N-[(2R,3S,4R,5R,8 ,10R,11R,12S,13S,14R)- ll-[[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木 糖基]氧基] -2-乙基 -3，4,10，13-四羟 -3，5，8，10，12，14-六甲基 -15-酮小氧-杂 -6-氮杂环十五垸 -13-基- 甲基] -苯甲酰胺  N-[(2R,3S,4R,5R,8,10R,11R,12S,13S,14R)- ll-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one -hetero-6-azacyclopentadepin-13-yl-methyl]-benzamide
Figure imgf000083_0001
Figure imgf000083_0001
将实施例 7中的 "环丙胺(2.43 !^，2.00 3511^101^ "改为使用 "苯甲酰胺 (2.43g)" ， 其余 同实施例 7。 最终得标题化合物 0.18g。  The "cyclopropylamine (2.43!^, 2.00 3511^101^" in Example 7 was changed to use "benzamide (2.43g)", and the rest was the same as in Example 7. The title compound was obtained.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 710[M+H]  ESI/MS: m/z 710[M+H]
实施例 151 Example 151
(2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(2,6-二氟 -苯基氨基） -甲基 ]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5,8，10,12,14-六甲基 -1-氧 -杂 -6-氮杂环十五烷 -15-酮  (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(2,6-difluoro-phenylamino)-methyl]-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
Figure imgf000083_0002
Figure imgf000083_0002
将实施例 7中的 "环丙胺 (2.43mL,2.00g,35mmoL)"改为使用 "2,6-二氟 -苯胺 (2.43mL)"， 其余同实施例 7。 最终得标题化合物 0.22g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to "2,6-difluoro-aniline (2.43 mL)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.22 g.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 718[M+H]  ESI/MS: m/z 718[M+H]
实施例 1S2Example 1S2
IUS^R^R^IUOiU lI SS S-MR ll-^AS-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -13-[N'-(2,4-二硝基-苯基) -肼基甲基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12，14-六甲基 -1-氧 -杂 -6-氮杂环十五垸 -15-酮  IUS^R^R^IUOiU lI SS S-MR ll-^AS-Trideoxy-3-(dimethylamino)-β-D-hexanopyranosyl]oxy] -13-[N'- (2,4-Dinitro-phenyl)-fluorenylmethyl]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl -1-oxo-hetero-6-azacyclopentadecane-15-one
82 82
替换页 （细则第 26条)
Figure imgf000084_0001
Replacement page (Article 26)
Figure imgf000084_0001
将实施例 121 中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "2,4-二硝基-苯肼"， 其余同 实施例 121。 最终得标题化合物 0.25g。  The "3-amino-4-ethynyl- 2H-pyrazole" in Example 121 was changed to use "2,4-dinitro-benzoquinone", and the rest were the same as in Example 121. The title compound was finally obtained in 0.25 g.
TLC ¾=0.44(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 787[M+H]十  ESI/MS: m/z 787[M+H]10
实施例 153 Example 153
(2R,3S，4R，5R,8R,10R，l lR，12S,13S，14R)-13-[(6-氯 -吡啶 -2-基-氨基) -甲基 ]-11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10,12,14-六甲基 -1-氧 -杂 -6-氮杂环十五烷 -15-酮  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(6-chloro-pyridin-2-yl-amino)-methyl]-11-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 ,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
Figure imgf000084_0002
Figure imgf000084_0002
将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "2-氨基 -6-氯-吡啶" ， 其余同 实施例 121。 最终得标题化合物 0.24g。  The "3-amino-4-ethynyl- 2H-pyrazole" in Example 121 was changed to use "2-amino-6-chloro-pyridine", and the rest were the same as in Example 121. The title compound was finally obtained in an amount of 0.24 g.
TLC Rj=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rj = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 717[M+H]十  ESI/MS: m/z 717[M+H] 十
实施例 Example
(2R,3S,4R,5R,8R，10R，l lR，12S，13S，14R)-13-[(6-溴 - P比啶 -2-基-氨基) -甲基 ]-11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5，8,10,12，14-六甲基小氧 -杂 -6-氮杂环十五垸 -15-酮  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(6-bromo-P-pyridin-2-yl-amino)-methyl]-11-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 ,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one
Figure imgf000084_0003
Figure imgf000084_0003
将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "2-氨基 -6-溴-吡啶"， 其余同 实施例 121。 最终得标题化合物 0.14g。  The "3-amino-4-ethynyl- 2H-pyrazole" in Example 121 was changed to use "2-amino-6-bromo-pyridine", and the rest was the same as in Example 121. The title compound was finally obtained in an amount of 0.14 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
83  83
替换页 （细则第 26条) ESI/MS: m/z 761[M+H]† Replacement page (Article 26) ESI/MS: m/z 761[M+H] †
实施例 155 Example 155
(2R,3S,4R,5R，8R,10R,l lR，12S,13S，14R)-ll-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -13-肼基甲基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-ll-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-13-mercaptomethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy -hetero-6-azacyclopentadecane-15-one
Figure imgf000085_0001
Figure imgf000085_0001
将实施例 9中的 "2-羟基 -3-甲基-苄胺"改为使用 "肼" ， 其余同实施例 9。 最终得标题 化合物 0.15g。  The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to "肼", and the rest was the same as in Example 9. The title compound was finally obtained in an amount of 0.15 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 621[M+H]  ESI/MS: m/z 621[M+H]
实施例 156 Example 156
(21，38，411，511,81 ,10 111，125，138,141 )-13-[(3-氨基-苄基氨基)-甲基]-11-[[3,4,6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8，10，12，14-六甲基小氧-杂 -6- 氮杂环十五垸 -15-酮  (21,38,411,511,81,10 111,125,138,141 )-13-[(3-Amino-benzylamino)-methyl]-11-[[3,4,6-trideoxy-3 -(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 - hexamethyloxy-hetero-6-azacyclopentadecane-15-one
Figure imgf000085_0002
Figure imgf000085_0002
将实施例 9中的 "2-羟基 -3-甲基-苄胺"改为使用 "3-氨基-苄氨"， 其余同实施例 9。 最 终得标题化合物 0.19g。  The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to use "3-amino-benzylamine", and the remainder was the same as in Example 9. The title compound was finally obtained in an amount of 0.19 g.
TLC ¾=0.44(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 711[M+H]十  ESI/MS: m/z 711[M+H] ten
实施例 1S7 Example 1S7
(2R，3S，4R,5R，8R，10R,l lR，12S,13S，14R)-13-[(2-氯 -苯基氨基) -甲基 ]-11-[[3,4，6-三脱氧 -3- (二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5，8,10，12，14-六甲基 -1-氧-杂 -6-氮 杂环十五烷 -15-酮  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-chloro-phenylamino)-methyl]-11-[[3,4,6- Triphos-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 ,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
Figure imgf000085_0003
Figure imgf000085_0003
84  84
替换页 （细则第 26条) 将实施例 7中的 "环丙胺 (2,43mL,2.00g，35mmoL)"改为使用 "2-氯苯氨 (2.43mL)"， 其 余同实施例 7。 最终得标题化合物 0.16g。 Replacement page (Article 26) The "cyclopropylamine (2, 43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "2-chlorophenylamine (2.43 mL)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.16 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 716[M+H]† ESI/MS: m/z 716[M+H] †
实施例 158 Example 158
(21 ,38，41 ,511;81，101，111 ,128，138,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基)-3-0-己吡喃木糖基] 氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-(Ν'-苯基 -肼基甲基) -1-氧-杂 -6-氮杂环 十五烷 -15-酮 (21, 38, 41, 511; 81,101,111, 128,138,1411) -11 - [[3,4,6-trideoxy-3- (dimethylamino) hexyl-pyrazol -3-0- Isokilyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(Ν'-phenyl- Mercaptomethyl)-1-oxo-hetero-6-azacyclopentadecane-15-one
Figure imgf000086_0001
Figure imgf000086_0001
将实施例 9中的 "2-羟基 -3-甲基-苄胺"改为使用 "苯肼"， 其余同实施例 9。 最终得标 题化合物 0.17g。  The "2-hydroxy-3-methyl-benzylamine" in Example 9 was changed to "benzoquinone", and the rest was the same as in Example 9. The title compound was finally obtained in 0.17 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 697[M+H]+ ESI/MS: m/z 697[M+H] +
实施例 159 Example 159
(2R，3S，4R，5R，8R,10R,l lR,12S，13S,14R)-ll-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 13-{[(1H-吲哚 -3-基-甲基) -氨基] -甲基 }-3,5,8，10,12，14-六甲基 -1- 氧-杂 -6-氣杂环十五垸 -15-酮 (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-ll-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy 13-{[(1H-indol-3-yl-methyl)-amino]-methyl}- 3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-acyclic heterocyclic fifteen-15-one
Figure imgf000086_0002
Figure imgf000086_0002
将实施例 7中的"环丙胺 (2.43mL,2.00g,35mmoL) "改为使用 " 1 H-吲哚 -3-基-甲胺 (2.43g) "， 其余同实施例 7。 最终得标题化合物 0.15g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "1H-indol-3-yl-methylamine (2.43 g)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.15 g.
TLC R产 0.44(二氯甲垸： 甲醇 =5:1)  TLC R yield 0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 735[M+H]十  ESI/MS: m/z 735[M+H] 十
实施例 160 Example 160
(2R，3S，4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4-氯 -2-硝基 -苯基氨基) -甲基 ]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10，13-四羟基 -3，5,8，10，12，14-六甲基小氧 -杂 -6-氮杂环十五垸 -15-酮  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4-chloro-2-nitro-phenylamino)-methyl]-11-[[3 ,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one
85 85
替换页 （细则第 26条)
Figure imgf000087_0001
Replacement page (Article 26)
Figure imgf000087_0001
将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "4-氯 -2-硝基-苯氨"， 其余同 实施例 121。 最终得标题化合物 0.14g。  The "3-amino-4-ethynyl- 2H-pyrazole" in Example 121 was changed to use "4-chloro-2-nitro-phenylamine", and the rest was the same as in Example 121. The title compound was finally obtained in an amount of 0.14 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 762[M+H]十  ESI/MS: m/z 762[M+H] 十
实施例 161 Example 161
(2¾33，411,51，81，1011,111，123，133，141 )-13-[(3-氯-正丙基氨基)-基]-11-[[3,4,6-三脱氧-3-(二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮 杂环十五烷 -15-酮  (23⁄433,411,51,81,1011,111,123,133,141)-13-[(3-chloro-n-propylamino)-yl]-11-[[3,4,6-trideoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
Figure imgf000087_0002
Figure imgf000087_0002
将实施例 7中的"环丙胺 (2.43mL，2.00g,35mmoL)"改为使用" 3-氯-正丙胺盐酸盐 (2.43g)"， 其余同实施例 7。 最终得标题化合物 0.17g。 The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to "3-chloro-n-propylamine hydrochloride (2.43 g)", and the rest was the same as in Example 7. The title compound was finally obtained in 0.17 g .
TLC Rf=0.44(二氯甲烷： 甲醇 -5:1)  TLC Rf = 0.44 (dichloromethane: methanol - 5:1)
ESI/MS: m/z 682[M+H]+ ESI/MS: m/z 682[M+H] +
实施例 162 Example 162
(2R,3S，4R,5R,8R，10R，l lR,12S，13S,14R)-13-[(2-氯 -4-硝基 -苯基氨基） -甲基 ]-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5，8,10,12,14-六甲基 -1-氧 -杂 -6-氮杂环十五烷 -15-酮  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-chloro-4-nitro-phenylamino)-methyl]-11-[[3 ,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
Figure imgf000087_0003
Figure imgf000087_0003
将实施例 7中的 "环丙胺 (2.43mL，2.00g,35mmoL)"改为使用 "2-氯 -4-硝基 -苯胺 (2.43g)"， 其余同实施例 7。 最终得标题化合物 0.18g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "2-chloro-4-nitro-aniline (2.43 g)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.18 g.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 761M+H]+ 替换页 （细则第 26条) 实施例 163 ESI/MS: m/z 761M+H] + replacement page (Article 26) Example 163
(2R，3S，4R，5R，8R，10R，l lR，12S，13S，14R)-ll-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -13-[(4-对 -甲基苯氧基 -苯基氨基) -甲 基] -1-氧*杂-6-氮杂环十五烷 -15-酮  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-ll-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(4-pair- Methylphenoxy-phenylamino)-methyl]-1-oxo-6 hetero-6-azacyclopentadecane-15-one
Figure imgf000088_0001
Figure imgf000088_0001
将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "4-对-甲基苯氧基-苯基胺"， 其余同实施例 121。 最终得标题化合物 0.24g。  The "3-amino-4-ethynyl- 2H-pyrazole" in Example 121 was changed to use "4-p-methylphenoxy-phenylamine", and the rest was the same as in Example 121. The title compound was finally obtained in an amount of 0.24 g.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 788 [M+H]+ ESI/MS: m/z 788 [M+H] +
实施例 164 Example 164
(21 ,38，4 51 ,811，10115111，128,133,1411)-13-[(3,5-二氯-吡啶-4-基-氨基)-甲基]-1 [[3,4,6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5，8，10，12,14-六甲基小 氧-杂 -6-氮杂环十五烷 -15-酮 (21,38,4 51 ,811,1011 5 111,128,133,1411)-13-[(3,5-dichloro-pyridin-4-yl-amino)-methyl]-1 [[3,4, 6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 ,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one
Figure imgf000088_0002
Figure imgf000088_0002
将实施例 7中的"环丙胺 (2.43mL，2.00g，35mmoL)"改为用 "3，5-二氯 -4-氨基 -吡啶 (2.43g)"， 其余同实施例 7。 最终得标题化合物 0.28g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to "3,5-dichloro-4-amino-pyridine (2.43 g)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.28 g.
TLC R|=0.44(二氯甲垸： 甲醇 =5:1)  TLC R|=0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 751 [M+H]+ ESI/MS: m/z 751 [M+H] +
实施例 165 Example 165
(2R,3S，4R，5R，8R,10R,l lR,12S，13S，14R)-13-[(3-氨基 -吡啶 -2-基-氨基) -甲基] - 11 -[[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5,8,10,12,14-六甲基小氧 -杂 -6-氮杂环十五'垸 -15-酮 （结构式见 (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3-amino-pyridin-2-yl-amino)-methyl] - 11 -[[[3 ,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000088_0003
Figure imgf000088_0003
替换页 （细则第 26条) 将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 "2， 3-二氨基-吡啶"， 其余同 实施例 121。 最终得标题化合物 0.26g。 Replacement page (Article 26) The "3-amino-4-ethynyl-2H-pyrazole" in Example 121 was changed to use "2,3-diamino-pyridine", and the rest was the same as in Example 121. The title compound was finally obtained in an amount of 0.26 g.
TLC R产 0.44(二氯甲垸： 甲醇 =5:1)  TLC R yield 0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 698 [M+H]+ ESI/MS: m/z 698 [M+H] +
实施例 166 Example 166
1-{(211,38,41，51，81，101，1111,128,138，141 )- [ 11-[[[3，4，6-三脱氧-3-(二甲基氨基)-3-0-己吡喃木 糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五'烷 -15-酮 -13- 基-甲基] -氨基 } -咪唑 -2,4-二酮 （结构  1-{(211,38,41,51,81,101,1111,128,138,141 )- [ 11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0 -hexylopyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6- Azacyclopentadecane-15-keto-13-yl-methyl]-amino}-imidazole-2,4-dione (structure
Figure imgf000089_0001
Figure imgf000089_0001
将实施例 121中的 "3-氨基 4-乙炔基 -2H-吡唑"改为使用 " 1-氨基 -2，4-咪唑二酮"， 其余 同实施例 121。 最终得标题化合物 0.28g。  The "3-amino-4-ethynyl- 2H-pyrazole" in Example 121 was changed to use "1-amino-2,4-imidazodione", and the rest of the same Example 121. The title compound was finally obtained in an amount of 0.28 g.
TLC RH).44(二氯甲垸： 甲醇 =5:1)  TLC RH).44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 704 [M+H]+ ESI/MS: m/z 704 [M+H] +
实施例 167 Example 167
(21 ,38，4¾51 ,81 ,1011,11 ，123,138，141 )-13-[(3,5-二甲氧基-苯基氨基)-甲基]-11-[[3，4，6-三脱氧(21,38,43⁄451 ,81 ,1011,11 ,123,138,141 )-13-[(3,5-Dimethoxy-phenylamino)-methyl]-11-[[3,4,6- Triphod
-3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12，14-六甲基 -15- 酮 -1_氧-杂 ·6-氮杂环十五垸 （结构式 -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 ,14-hexamethyl-15-one-1_oxy-hetero- 6 -nitrohelidene fifteen fluorene (structural formula
Figure imgf000089_0002
Figure imgf000089_0002
将实施例 121 中的 "3-氨基 4-乙炔基 -2Η-吡唑"改为使用 "3，5-二甲氧基-苯胺"， 且将 反应容器由 " lOOmL圆底烧瓶"改为密封试管，其余同实施例 121。最终得标题化合物 0.22g。  The "3-amino-4-ethynyl-2-indole-pyrazole" in Example 121 was changed to use "3,5-dimethoxy-aniline", and the reaction vessel was changed from "100 mL round bottom flask" to sealed. The test tube was the same as in Example 121. The title compound was finally obtained in an amount of 0.22 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 742 [M+H]十  ESI/MS: m/z 742 [M+H] 十
实施例 168 Example 168
3-{(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)- [ 11-[[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5，8，10,12，14-六甲基 -15-酮小氧-杂 -6-氮杂环十 五垸 -13-基-甲基] -氨基 } -噻吩 -2-羧酸甲酯； （结构式见下）  3-{(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-[ 11-[[3,4,6-Trideoxy-3-(dimethylamino)- β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one Methyl oxy-hetero-6-azetidine pentadepin-13-yl-methyl]-amino}-thiophene-2-carboxylate; (see below for structural formula)
88 88
替换页 （细则第 26条)
Figure imgf000090_0001
Replacement page (Article 26)
Figure imgf000090_0001
将实施例 7中的 "环丙胺(2.43mL，2.00g，35mmOL)"改为使用 "3-氨基 -2-噻吩甲酸甲酯 (2.43mL)"， 其余同实施例 7。 最终得标题化合物 0.12g。 The "cyclopropylamine (2.43 mL, 2.00 g, 35 mm O L)" in Example 7 was changed to use "methyl 3-amino-2-thiophenecarboxylate (2.43 mL)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.12 g.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 745 [M+H]+ ESI/MS: m/z 745 [M+H] +
实施例 169 Example 169
(2R,3S,4 ,5R,8R,10 ,l lR,12S,13S,14R)-13-{[3-氯 -1-(2-氯 -乙基） -正丙基氨基 ] - 甲 基}-11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5，8，10,12,14-六甲基小氧-杂 -6-氮杂 见下）  (2R,3S,4,5R,8R,10,l lR,12S,13S,14R)-13-{[3-chloro-1-(2-chloro-ethyl)-n-propylamino] - methyl }-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10, 13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-aza see below
Figure imgf000090_0002
Figure imgf000090_0002
将实施例 121中的" 3-氨基 4-乙炔基 -2H-吡唑"改为使用" 3-氯 -1-(2-氯-乙基) -正丙基胺"， 且将反应容器由 " lOOmL圆底烧瓶"改为 "50mL圆底烧瓶"， 其余同实施例 121。 最终得标 题化合物 0.16g。  The "3-amino-4-ethynyl-2H-pyrazole" in Example 121 was changed to use "3-chloro-1-(2-chloro-ethyl)-n-propylamine", and the reaction vessel was The "100 mL round bottom flask" was changed to "50 mL round bottom flask", and the rest was the same as in Example 121. The title compound was finally obtained in 0.16 g.
TLC RH).44(二氯甲烷： 甲醇 =5:1)  TLC RH).44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 699 [M+H]十  ESI/MS: m/z 699 [M+H] 十
实施例 170 Example 170
(2 ,38，4! ,51 ,81，101，111，128，138,141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10，13-四羟基 -13-[(3-羟基-吡啶 -2-基-氨基) -甲基 ]-3,5，8,10，12,14-六甲基小氧- 杂 -6-氮杂环十五烷 -15-酮 （结构式见  (2,38,4!,51,81,101,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexanpyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-hydroxy-pyridin-2-yl-amino)-methyl]-3,5,8 ,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see structure)
Figure imgf000090_0003
Figure imgf000090_0003
将实施例 7中的"环丙胺 (2.43mL,2.00g,35mmoL)"改为使用" 2-氨基 -3-羟基-吡啶 (2.43g)"， 其余同实施例 7。 最终得标题化合物 0.15g。  The "cyclopropylamine (2.43 mL, 2.00 g, 35 mmoL)" in Example 7 was changed to use "2-amino-3-hydroxy-pyridine (2.43 g)", and the rest was the same as in Example 7. The title compound was finally obtained in an amount of 0.15 g.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 699 [M+H]+ 替换页 （细则第 26条) 实施例 171 ESI/MS: m/z 699 [M+H] + replacement page (Article 26) Example 171
(21 ,38,41，51 ,81 ,101 ,111 ,128,138，14] )-11-[[3,4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3，4,10，13-四羟基 -13-异丙基 -硫基 -甲基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环 十五垸 -15-酮 （结构式见下）  (21,38,41,51,81,101,111,128,138,14] )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexanpyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-isopropyl-thio-methyl-3,5,8,10,12,14-hexa Keith-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000091_0001
Figure imgf000091_0001
将 500mg上述通式 6化合物溶于 5mL甲苯中。 向其中加入过量 K2C03和 0.7mL异丙硫 醇。 60°C下反应 46h, 经 TLC检测反应完毕。 加入饱和 NaHC03停止反应， 用 3x50mL二氯 甲烷萃取， 合并有机相， 用无水硫酸钠干燥、 过滤、 滤液浓缩蒸千得粗品。 用硅胶柱色谱进 一步纯化（二氯甲垸： 甲醇： 氨水 =100:2:0.2) 得 0.12g标题化合物。 500 mg of the above compound of the formula 6 was dissolved in 5 mL of toluene. An excess of K 2 CO 3 and 0.7 mL of isopropyl mercaptan were added thereto. The reaction was carried out at 60 ° C for 46 h, and the reaction was completed by TLC. Saturated NaHC0 3 was added to stop the reaction, and extracted with 3x50mL dichloromethane and the combined organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product was distilled one thousand. Further purification by silica gel column chromatography (dichloromethane:methanol:methanol=100:2:0.2)
TLC R产 0.44(二氯甲垸： 甲醇 =5:1)  TLC R yield 0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 665 [M+H]十  ESI/MS: m/z 665 [M+H] 十
实施例 172 Example 172
(21，38,411，51 ,81 ,101^111，128，138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)- -0-己吡喃木糖基] 氧基] -2-乙基 -3，4,10，13-四羟基 -13- (叔丁基-硫基） 甲基 -3，5,8，10,12,14-六甲基 -1-氧-杂 -6-氮杂 环十五垸 -15-酮 （结构式见下）  (21,38,411,51 ,81 ,101^111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-o-hexanopyryl) Oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(tert-butyl-thio)methyl-3,5,8,10,12,14-hexamethyl-1 -Oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000091_0002
Figure imgf000091_0002
将实施例 171中的 "异丙硫醇"改为使用 "叔丁硫醇"， 其余同实施例 171。 最终得标 题化合物 0.17g。  The "isopropyl thiol" in Example 171 was changed to "t-butyl mercaptan", and the rest was the same as in Example 171. The title compound was finally obtained in 0.17 g.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 679 [M+H]  ESI/MS: m/z 679 [M+H]
实施例 173 Example 173
(211,33,41，511，81，1011，1111，128,133，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3，4，10，13-四经基 -3，5,8，10，12，14-六甲基 -13- (萘 -2-基-硫甲基)小氧-杂 -6-氮杂环十 五烷 -15-酮（结构式见下）  (211, 33, 41, 511, 81, 1011, 1111, 128, 133, 141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetramyl-3,5,8,10,12,14-hexamethyl-13-(naphthalen-2-yl-sulfur Methyl) small oxygen-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000091_0003
Figure imgf000091_0003
90  90
替换页 （细则第 26条) 将实施例 17】中的 "异丙硫醇"改为使用 "2-萘硫醇"， 其余同实施例 r ira ^得标题 化合物 0.14g。 Replacement page (Article 26) The "isopropyl thiol" in Example 17 was changed to use "2-naphthylthiol", and the rest of the same Example r ira gave the title compound 0.14 g.
TLC Rf0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 749 [M+H]十  ESI/MS: m/z 749 [M+H] 十
实施例 174 Example 174
(2R,3 S,4R,5R,8R, 10R， 11 R, 12S, 13 S， 14R)- 13-(4,5-二氢 -噻唑 -2-基-硫甲基) - 11 -[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5，8，10,12,14-六甲基小氧 -杂 -6-氮杂环十五浣 -15-酮 （结构式见  (2R,3 S,4R,5R,8R, 10R, 11 R, 12S, 13 S, 14R)- 13-(4,5-Dihydro-thiazol-2-yl-thiomethyl) - 11 -[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 ,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000092_0001
Figure imgf000092_0001
将实施例 171中的 "异丙硫醇"改为使用 "2-硫噻唑啉" ， 且反应时间由 46h改为 50h, 其余同实施例 171。 最终得标题化合物 0.13g。  The "isopropylthiol" in Example 171 was changed to use "2-thiothiazoline", and the reaction time was changed from 46h to 50h, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.13 g.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 708 [M+H]+ ESI/MS: m/z 708 [M+H] +
实施例 175 Example 175
(2R,3S，4R,5R,8R,10R,l lR，12S，13S，14R)-13-(2，3-二羟基 -丙基 -硫基 -甲基 )-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基- -3,5,8,10,12,14-六甲基 -1- 氧-杂 -6-氮杂环十五烷 -15-酮 （结构式 (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-(2,3-dihydroxy-propyl-thio-methyl)-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy--3,5 ,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (structural formula
Figure imgf000092_0002
Figure imgf000092_0002
将实施例 171中的 "异丙硫醇"改为使用 " 1-硫甘油"， 且反应时间由 46h改为 50h, 其 余同实施例 171。 最终得标题化合物 0.16g。  The "isopropylthiol" in Example 171 was changed to "1-thioglycerol", and the reaction time was changed from 46h to 50h, which is the same as in Example 171. The title compound was finally obtained in an amount of 0.16 g.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 697 [M+H]+ ESI/MS: m/z 697 [M+H] +
实施例 176 Example 176
(2 ,38，4! ,51，81，101，111，128，138，141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基)-3-0-己吡喃木糖基] 氧基] -2-乙基 -13- (呋喃 -2-基-甲基-硫基-甲基) -3，4，10,13-四羟基 -3,5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五院 -15-酮 （结构式见下）  (2,38,4!,51,81,101,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyl Pyranopyranyl]oxy]-2-ethyl-13-(furan-2-yl-methyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8 ,10,12,14-hexamethyloxy-hetero-6-azetidine fifteenth hospital-15-ketone (see below for structural formula)
91 91
替换页 （细则第 26条)
Figure imgf000093_0001
Replacement page (Article 26)
Figure imgf000093_0001
将实施例 171中的 "异丙硫醇"改为使用 "糠 (基)硫醇" ， 且反应时间由 46h改为 48h， 其余同实施例 171。 最终得标题化合物 0.15g。  The "isopropyl thiol" in Example 171 was changed to use "mercapto thiol", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.15 g.
TLC Rj=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rj = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 703 [M+H]+ ESI/MS: m/z 703 [M+H] +
实施例 177 Example 177
(2R,3S，4R，5R，8R，10R，l lR，12S，13S，14R)-13-(2-二乙基氨基-乙基-硫甲基 )-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8,10,12,14-六甲基小氧 -杂 -6-氮杂环十五垸 -15酮 （结构式见  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-(2-diethylamino-ethyl-thiomethyl)-11-[[3,4,6 -triptylo-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15 ketone (see structure formula)
Figure imgf000093_0002
Figure imgf000093_0002
将实施例 171中的 "异丙硫醇"改为使用 "2-二乙氨基乙硫醇"， 且反应时间由 46h改 为 50h， 其余同实施例 171。 最终得标题化合物 0.12g。  The "isopropyl thiol" in Example 171 was changed to use "2-diethylaminoethanethiol", and the reaction time was changed from 46h to 50h, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.12 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 722 [M+H]十  ESI/MS: m/z 722 [M+H] 十
塞 Plug
(211,38，411,51 ,81 ,1011，111 ,128，138，141 )-13-苄基-硫基-甲基-11-[[3，4，6-三脱氧-3-(二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12，14-六甲基小氧-杂 -6-氮杂环 十五烷 -15-酮 （结构式见下）  (211, 38, 411, 51, 81, 1011, 111, 128, 138, 141)-13-benzyl-thio-methyl-11-[[3,4,6-trideoxy-3-(di) Methylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexa Small oxygen-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000093_0003
Figure imgf000093_0003
将实施例 171中的 "异丙硫醇"改为使用 "苄硫醇"， 且反应时间由 46h改为 48h， 其 余同实施例 171。 最终得标题化合物 0.14g。  The "isopropyl thiol" in Example 171 was changed to "benzyl thiol", and the reaction time was changed from 46h to 48h, which is the same as in Example 171. The title compound was finally obtained in an amount of 0.14 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 713 [M+H]+ ESI/MS: m/z 713 [M+H] +
实施例 179 替换页 （细则第 26条) (21，33，41 ,51 ,811,101 ,111 ,128,138,141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-对-甲基苯-硫基-甲基小氧-杂 -6-氮杂 环十五垸 -15-酮 （结构式见下） Example 179 Replacement Page (Rule 26) (21,33,41,51,811,101,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-l-hexyranose]oxygen -2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-p-methylbenzene-thio-methyloxygen -hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000094_0001
Figure imgf000094_0001
将实施例 171中的 "异丙硫醇"改为使用 "4-甲苯硫酚" ， 且反应时间由 46h改为 48h, 其余同实施例 171。 最终得标题化合物 0.16g。  The "isopropyl thiol" in Example 171 was changed to "4-toluene thiol", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.16 g.
TLC Ri=0.44(二氯甲垸： 甲醇 =5:1)  TLC Ri=0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 713 [M+H]+ ESI/MS: m/z 713 [M+H] +
实施例 180 Example 180
(21 ,33，411,511,81，101 ,111 ,123,138,141 )-13-(4-氯-苯基-硫基-甲基)-11-[ (4-二甲基氨基 -3-羟基 -6-甲基 -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮 杂环十五浣 -15-酮 （结构式见下）  (21,33,411,511,81,101,111,123,138,141)-13-(4-chloro-phenyl-thio-methyl)-11-[(4-dimethylamino-3-hydroxy-6- Methyl-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl Oxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000094_0002
Figure imgf000094_0002
将实施例 171中的 "异丙硫醇"改为使用 "4-氯苯硫酚"， 且反应时间由 46h改为 48h， 其余同实施例 171。 最终得标题化合物 0.17g。  The "isopropyl thiol" in Example 171 was changed to "4-chlorothiophenol", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in 0.17 g.
TLC R尸 0.44(二氯甲烷： 甲醇 =5:1)  TLC R corpse 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 733 [M+H]十  ESI/MS: m/z 733 [M+H] 十
实施例 181 Example 181
(21 ,38，41 ,51 ,81 ,101，1111,128，133,14 -11-[[3，4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8,10,12,14-六甲基 -13-正丙基 -硫基 -甲基小氧-杂 -6-氮杂环 十五垸 -15-酮 （结构式见下）  (21,38,41,51,81,101,1111,128,133,14 -11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexanpyran) Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-n-propyl-thio-methyl Small oxygen-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000094_0003
Figure imgf000094_0003
将实施例 171中的 "异丙硫醇"改为使用 "丙硫醇" ， 且反应时间由 46h改为 48h， 其 余同实施例 171。 最终得标题化合物 0.14g。 替换页 （细则第 26条) TLC ¾=0.44(二氯甲垸： 甲醇 =5:1) The "isopropyl thiol" in Example 171 was changed to use "propanethiol", and the reaction time was changed from 46h to 48h, and the rest was the same as in Example 171. The title compound was finally obtained in an amount of 0.14 g. Replacement page (Article 26) TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 665 [M+H]+ ESI/MS: m/z 665 [M+H] +
实施例 182 Example 182
3-{(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)- 11-[[3，4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖 基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5,8,】0，12，14-六甲基-15-酮-l-氧-杂-6-氮杂环十五垸-13-基- 甲基-硫基}-丙酸 (结构式见下）  3-{(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)- 11-[[3,4,6-Trideoxy-3-(dimethylamino)-indole- 0-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,0,12,14-hexamethyl-15-one- L-Oxo-hetero-6-azacyclopentadecane-13-yl-methyl-thio}-propionic acid (see below for structural formula)
Figure imgf000095_0001
Figure imgf000095_0001
将实施例 171中的 "异丙硫醇"改为使用 "3-硫醇丙酸"， 且反应时间由 46h改为 50h， 其余同实施例 171。 最终得标题化合物 0.28g。  The "isopropyl thiol" in Example 171 was changed to use "3-thiol propionic acid", and the reaction time was changed from 46h to 50h, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.28 g.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 695 [M+H]  ESI/MS: m/z 695 [M+H]
实施例 183 Example 183
(211，33,4 511，81，101，1111，128，138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基) 0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12，14-六甲基 -13-苯基 -硫基 -甲基小氧-杂 -6-氮杂环十 五垸 -15-酮 （结构式见下）  (211,33,4 511,81,101,1111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino) 0-hexylopyranosyl] Oxygen -2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-phenyl-thio-methyloxy-hybrid- 6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000095_0002
Figure imgf000095_0002
将实施例 171中的 "异丙硫醇"改为使用 "苯硫酚"， 且反应时间由 46h改为 48h, 其 余同实施例 171。 最终得标题化合物 0.18g。  The "isopropylthiol" in Example 171 was changed to "thiophenol", and the reaction time was changed from 46h to 48h, which is the same as in Example 171. The title compound was finally obtained in an amount of 0.18 g.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 699 [M+H]  ESI/MS: m/z 699 [M+H]
实施例 184 Example 184
(2R,3 S,4R,5R,8R, 10R,11R,12S,13S，14R)-13- (丁基-硫基-甲基) - 11 -[[3,4,6-三脱氧 -3- (二甲基氨 基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟 -3,5，8,10，12,14-六甲基 -1-氧-杂 -6-氮杂环十 五烷 -15-酮（结构式见下）  (2R,3 S,4R,5R,8R,10R,11R,12S,13S,14R)-13-(butyl-thio-methyl)-11-[[3,4,6-trideoxy-3 - (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 - hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000095_0003
替换页 （细则第 26条) 将实施例 171中的 "异丙硫醇"改为使用 "丁硫醇" ， 且反应时间由 46h改为 40h， 其 余同实施例 171。 最终得标题化合物 0.15g
Figure imgf000095_0003
Replacement page (Article 26) The "isopropyl thiol" in Example 171 was changed to "butyl thiol", and the reaction time was changed from 46h to 40h, and the rest was the same as in Example 171. The title compound was finally obtained 0.15g
TLC ¾=0.44(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z679[M+H]+ ESI/MS: m/z679[M+H] +
实施例 185 Example 185
(21,3841，51,81 101,111,128,1381411)-11-[[346-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3410,13-四羟基 -13-(3-硫醇-丙基-硫基-甲基) -3,5,8,10,12,14-六甲基 -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  (21,3841,51,81 101,111,128,1381411)-11-[[346-Trideoxy-3-(dimethylamino)-indole-0-hexyranoxy]oxy]-2-ethyl -3410,13-tetrahydroxy-13-(3-thiol-propyl-thio-methyl)-3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6- Nitroheterocyclopentadecano-15-one (see below for structural formula)
Figure imgf000096_0001
Figure imgf000096_0001
将实施例 171中的 "异丙硫醇"改为使用 "1,3-丙二硫醇"， 且反应时间由 46h改为 40h, 其余同实施例 171。 最终得标题化合物 0.17g  The "isopropyl thiol" in Example 171 was changed to "1,3-propanedithiol", and the reaction time was changed from 46h to 40h, and the rest were the same as in Example 171. The title compound was finally obtained. 0.17g
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z697 [M+H]  ESI/MS: m/z697 [M+H]
实施例 186 Example 186
(211,38,41^51 81 101,111,1231381411)-11-[[3,46-三脱氧-3-(二甲基氨基)-3-0-己吡喃木糖基] 氧基] -2-乙基 -3,41013-四羟基 -3581012,14-六甲基 -13-戊基-硫基-甲基小氧-杂 -6-氮杂环十 五垸 -15-酮 （结构式见下） (211,38,41^51 81 101,111,1231381411)-11-[[3,46-Trideoxy-3-(dimethylamino)-3-0-hexylpyranosyl]oxy] -2 -ethyl-3,41013-tetrahydroxy-3581012,14-hexamethyl-13-pentyl-thio-methyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula) )
Figure imgf000096_0002
Figure imgf000096_0002
将实施例 171中的 "异丙硫醇"改为使用 "1-戊硫醇"， 且反应时间由 46h改为 48h， 其 余同实施例 171。 最终得标题化合物 0.16g  The "isopropyl thiol" in Example 171 was changed to use "1-pentanethiol", and the reaction time was changed from 46h to 48h, which is the same as Example 171. The title compound was finally obtained. 0.16g
TLC ¾=0.44(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z693 [M+H]  ESI/MS: m/z693 [M+H]
实施例 187 Example 187
(211,33411)51181 101?11 ,1281331411)-11-[[346-三脱氧-3-(二甲基氨基)- -0-己吡喃木糖基] 氧基] -2-乙基 -34,1013-四羟基 -358,1012,14-六甲基 -13- (己基-硫基-甲基） -1-氧-杂 -6-氮杂环 十五垸 -15-酮 （结构式见下） (211,33411 ) 51181 101 ? 11 ,1281331411)-11-[[346-Trideoxy-3-(dimethylamino)- -0-hexylopyranosyl]oxy]-2-ethyl- 34,1013-tetrahydroxy-358,1012,14-hexamethyl-13-(hexyl-thio-methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one (see structure formula) under)
95 95
替换页 （细则第 26条)
Figure imgf000097_0001
Replacement page (Article 26)
Figure imgf000097_0001
将实施例 171中的 "异丙硫醇"改为使用 " 1-己硫醇"， 且反应时间由 46h改为 48h， 其 余同实施例 171。 最终得标题化合物 0.14g。  The "isopropyl thiol" in Example 171 was changed to use "1-hexanethiol", and the reaction time was changed from 46h to 48h, which is the same as Example 171. The title compound was finally obtained in an amount of 0.14 g.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 707 [M+H]+ ESI/MS: m/z 707 [M+H] +
实施例 lp8 Example lp8
(21，38，41，51，81，101 ,11¾128，138,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8,10，12，14-六甲基 -13- (辛基-硫基-甲基）小氧-杂 -6-氮杂环 十五烷 -15-酮 （结构式见下）  (21,38,41,51,81,101,113⁄4128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-indole-0-hexyranose ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(octyl-thio-methyl) small Oxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000097_0002
Figure imgf000097_0002
将实施例 171中的 "异丙硫醇"改为使用 " 1-辛硫醇"， 且反应时间由 46h改为 48h， 其 余同实施例 171。 最终得标题化合物 0.15g。  The "isopropyl thiol" in Example 171 was changed to use "1-octyl thiol", and the reaction time was changed from 46h to 48h, which is the same as Example 171. The title compound was finally obtained in an amount of 0.15 g.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 735 [M+H]+ ESI/MS: m/z 735 [M+H] +
实施例 189 Example 189
(21，38，411,51，811，1011,11^128,138，1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基)- -0-己吡喃木糖基] 氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10,12,14-六甲基 -13-十二垸基 -硫基 -甲基 -1-氧-杂 -6-氮杂 环十五焼 -15-酮 （结构式见下  (21,38,411,51,811,1011,11^128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)--0-hexyryl xylose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-dodecyl-thio-methyl -1-Oxo-hetero-6-nitrohecyclopentadecane-15-one (see below for structural formula)
Figure imgf000097_0003
Figure imgf000097_0003
将实施例 171中的 "异丙硫醇"改为使用 "十二硫醇"， 且反应时间由 46h改为 48h， 其余同实施例 171。 最终得标题化合物 0.17g。  The "isopropyl thiol" in Example 171 was changed to "dodecyl mercaptan", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in 0.17 g.
TLC RH).44(二氯甲烷： 甲醇 =5:1)  TLC RH).44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 792 [M+H]+ ESI/MS: m/z 792 [M+H] +
实施例 190 替换页 （细则第 26条) (2R，3S，4R,5R,8R,10R,l lR，12S,13S,14R)-ll-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 1-13-(3-氟-苄基-硫基-甲基) -3,4，10，13-四羟基 -3，5，8,10，12，14-六甲基小氧-杂 -6-氮 杂环十五垸 -15-酮 （结构式见下） Example 190 Replacement Page (Rule 26) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-ll-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl1-13-(3-fluoro-benzyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000098_0001
Figure imgf000098_0001
将实施例 171中的"异丙硫醇"改为使用 "间氟苯甲硫醇"，且反应时间由 46h改为 48h, 其余同实施例 171。 最终得标题化合物 0.17g。  The "isopropyl thiol" in Example 171 was changed to "m-fluorobenzothiol", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in 0.17 g.
TLC 11尸0.44(；二氯甲烷： 甲醇 =5:1)  TLC 11 corpse 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 731 [M+H]+ ESI/MS: m/z 731 [M+H] +
实施例 191 Example 191
(21 ,38,41 ,51，81，101，1111,128,138,141 )-13-(苯并噻唑-2-基-硫基-甲基)-11-[[3,4,6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  (21,38,41,51,81,101,1111,128,138,141)-13-(benzothiazol-2-yl-thio-methyl)-11-[[3,4,6-trideoxy-3 -(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 -hexamethyl-1-oxo-6-nitrozacyclopentadecane-15-one (see below for structural formula)
Figure imgf000098_0002
Figure imgf000098_0002
将实施例 171中的 "异丙硫醇"改为使用 "2-巯基苯并噻唑" ， 且反应时间由 46h改为 48h, 其余同实施例 171。 最终得标题化合物 0.18g。  The "isopropyl thiol" in Example 171 was changed to "2-mercaptobenzothiazole", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.18 g.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 757 [M+H]十  ESI/MS: m/z 757 [M+H] 十
实施例 1 Example 1
{(2R，3S,4R,5R,8R,10R,11R,12S，13S,14R)-1卜 [[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-木 -吡喃 糖基） ]-2-氧 -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12，14-六甲基 -15-酮 -1-氧-杂 -6-氮杂环十五 垸 -13-基-甲基-硫基] 乙酸 （结构式  {(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-1Bu [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-木-pyranosyl)]-2-oxo-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one-1- Oxy-hetero-6-nitrohecyclopentadepin-13-yl-methyl-thio]acetic acid (structural formula
Figure imgf000098_0003
Figure imgf000098_0003
将实施例 171中的 "异丙硫醇"改为使用 "硫乙醇酸"， 且反应时间由 46h改为 48h， 其余同实施例 171。 最终得标题化合物 0.48g。  The "isopropyl thiol" in Example 171 was changed to "thioglycolic acid", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in 0.48 g.
Rf=0.34(二氯甲垸： 甲醇 =5:1) 替换页 （细则第 26条) ESI/MS: m/z681 [M+H] Rf = 0.34 (dichloromethane: methanol = 5:1) Replacement page (Article 26) ESI/MS: m/z681 [M+H]
实施例 193 Example 193
(2R,3S4R,5R,8R,10R,11R,12S,13S,14R)-11-[[346-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -13-(4-氟-苯基-硫基) -3,4,10,13-四羟基 -35,8101214-六甲基 -1-氧-杂 -6-氮杂环十 五垸 -15-酮 （结构式见下）  (2R,3S4R,5R,8R,10R,11R,12S,13S,14R)-11-[[346-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl] Oxygen 2-ethyl-13-(4-fluoro-phenyl-thio)-3,4,10,13-tetrahydroxy-35,8101214-hexamethyl-1-oxo-hetero-6-nitrogen Heterocyclic fifteen-15-one (see below for structural formula)
Figure imgf000099_0001
Figure imgf000099_0001
将实施例 171中的 "异丙硫醇"改为使用 "4-氟苯硫酚"， 且反应时间由 46h改为 48h 其余同实施例 171。 最终得标题化合物 0.23g  The "isopropyl thiol" in Example 171 was changed to "4-fluorothiophenol", and the reaction time was changed from 46h to 48h, and the rest of the same Example 171. The title compound was finally obtained 0.23g
TLC ¾=0.39(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.39 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 717 [M+H]  ESI/MS: m/z 717 [M+H]
实施例 194 Example 194
(21,38,41 51 81,1011111 128138141)-11-[[346-三脱氧-3-(二甲基氨基) -0-己吡喃木糖基] 氧基] -2-乙基 -341013-四羟基 -13- (异丁基-硫基-甲基） -35,8,1012,14-六甲基 -1-氧-杂 -6-氮杂 环十五垸 -15-酮 （结构式见下）  (21,38,41 51 81,1011111 128138141)-11-[[346-Trideoxy-3-(dimethylamino)-0-hexylopyranosyl]oxy]-2-ethyl-341013 -tetrahydroxy-13-(isobutyl-thio-methyl)-35,8,1012,14-hexamethyl-1-oxo-6-nitrozacyclopentadecane-15-one (structural formula See below)
Figure imgf000099_0002
Figure imgf000099_0002
将实施例 171中的 "异丙硫醇"改为使用 "异丁硫醇"， 且反应时间由 46h改为 48h 其余同实施例 171。 最终得标题化合物 0.14g  The "isopropyl thiol" in Example 171 was changed to use "isobutyl mercaptan", and the reaction time was changed from 46h to 48h, and the rest of the same example 171. The title compound was finally obtained.
TLC Rf=0.40(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.40 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z679[M+H]  ESI/MS: m/z679[M+H]
实施例 1»S Example 1»S
(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R) - 11-[[346-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -341013-四羟基 -13-{ (仲-丁基-硫基） -甲基 }-358101214-六甲基 -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R) - 11-[[346-Trideoxy-3-(dimethylamino)-β-D-hexylpyranose ]oxy]-2-ethyl-341013-tetrahydroxy-13-{(sec-butyl-thio)-methyl}-358101214-hexamethyl-1-oxo-hetero-6-azetidine Wuqi-15-ketone (see below for structural formula)
Figure imgf000099_0003
Figure imgf000099_0003
98  98
替换页 （细则第 26条) 将实施例 171中的 "异丙硫醇"改为使用 "仲丁硫醇" ， 且反应时间由 46h改为 48h 其余同实施例 171。 最终得标题化合物 0.13g Replacement page (Article 26) The "isopropyl thiol" in Example 171 was changed to use "sec-butyl mercaptan", and the reaction time was changed from 46h to 48h. The title compound was finally obtained 0.13g
TLC R产 0.44(二氯甲垸： 甲醇 =5:1)  TLC R yield 0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 679[M+H]+ ESI/MS: m/z 679[M+H] +
实施例 196 Example 196
(21 38,41 511,811,101,1111,123138,1411)-11-[[346-三脱氧-3-(二甲基氨基) -0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -13-(2-硫醇-乙基-硫基-甲基) -3,5,81012,14-六甲基 -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  (21 38,41 511,811,101,1111,123138,1411)-11-[[346-Trideoxy-3-(dimethylamino)-0-hexylopyranosyl]oxy]-2-ethyl- 3,4,10,13-tetrahydroxy-13-(2-thiol-ethyl-thio-methyl)-3,5,81012,14-hexamethyl-1-oxo-hetero-6-nitrogen Heterocyclic fifteen-15-one (see below for structural formula)
Figure imgf000100_0001
Figure imgf000100_0001
将实施例 171中的 "异丙硫醇"改为使用 "1,2-乙二硫醇"， 且反应时间由 46h改为 48h 其余同实施例 171。 最终得标题化合物 0.14g  The "isopropyl thiol" in Example 171 was changed to use "1,2-ethanedithiol", and the reaction time was changed from 46h to 48h, and the rest of the same Example 171. The title compound was finally obtained.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z683[M+H]  ESI/MS: m/z683[M+H]
实施例 197 Example 197
(2R,3S,4R,5R,8R,10R,llR,12S13S14R)-ll-[[346-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -34,1013-四羟基 -35,8,10,1214-六甲基 -13-(3-甲基-丁基-硫基-甲基) -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下） (2R,3S,4R,5R,8R,10R,llR,12S13S14R)-ll-[[346-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy] -2-ethyl-34,1013-tetrahydroxy-35,8,10,1214-hexamethyl-13-(3-methyl-butyl-thio-methyl)-1-oxo-hetero-6 - Nitrozacyclopentadecane-15-one (see below for structural formula)
Figure imgf000100_0002
Figure imgf000100_0002
将实施例 171中的 "异丙硫醇"改为使用 "异戊硫醇"， 且反应时间由 46h改为 48h, 其余同实施例 171。 最终得标题化合物 0.12g  The "isopropyl thiol" in Example 171 was changed to "isopentyl thiol", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained 0.12g
TLC Rj=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rj = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z694[M+H]  ESI/MS: m/z 694 [M+H]
实施例 198 Example 198
P! S^R^R^F OF lfUSSJSSJAiq-n-ClH-苯并咪唑 -2-基-硫基-甲基) -11-[[34,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -341013-四羟基 -35,810,1214-六甲基 -1-氧 -杂 -6-氮杂环十五烷 -15-酮 （结构式见下）  P! S^R^R^F OF lfUSSJSSJAiq-n-ClH-benzimidazol-2-yl-thio-methyl) -11-[[34,6-trideoxy-3-(dimethylamino) -β-D-hexylpyranosyl]oxy]-2-ethyl-341013-tetrahydroxy-35,810,1214-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15 -ketone (see below for structural formula)
99 99
替换页 （细则第 26条)
Figure imgf000101_0001
Replacement page (Article 26)
Figure imgf000101_0001
将实施例 171中的 "异丙硫醇"改为使用 "2-巯基苯并咪唑" ， 且反应时间由 46h改为 48h， 其余同实施例 171。 最终得标题化合物 0.1 lg。  The "isopropyl thiol" in Example 171 was changed to "2-mercaptobenzimidazole", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained as 0.1 lg.
TLC R产 0.44(二氯甲烷： 甲醇 =5:1)  TLC R yield 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 739[M+H]十  ESI/MS: m/z 739[M+H] 十
实施例 199 Example 199
(21 ，38,4 51^，81^101 ，1111,128，138，141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基) -0-己吡喃木糖基] 氧基] -2-乙基 -3，4,10，13-四羟基 -13-(4-羟基-苯基-硫基-甲基) -3,5，8，10,12，14-六甲基 -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  (21,38,4 51^,81^101,1111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranium Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(4-hydroxy-phenyl-thio-methyl)-3,5,8,10,12, 14-hexamethyl-1-oxo-6-nitrozacyclopentadecane-15-one (see below for structural formula)
Figure imgf000101_0002
Figure imgf000101_0002
将实施例 171中的 "异丙硫醇"改为使用 "4-羟基苯硫酚"，且反应时间由 46h改为 48h， 其余同实施例 171。 最终得标题化合物 0.19g。  The "isopropyl thiol" in Example 171 was changed to "4-hydroxythiophenol", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.19 g.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 715[M+H]十  ESI/MS: m/z 715[M+H] 十
实施例 200 Example 200
(21 ，38,411，51 ,81 ,101 ，111 ，128,138，141 )-13-[(烯丙基-硫基)-甲基]-11-[[3，4,6-三脱氧-3-(二甲基 氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12，14-六甲基 -1-氧-杂 -6-氮杂 环十五焼 -15-酮 （结构式见下）  (21,38,411,51,81,101,111,128,138,141)-13-[(allyl-thio)-methyl]-11-[[3,4,6-trideoxy-3-( Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-six Methyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000101_0003
Figure imgf000101_0003
将实施例 171中的 "异丙硫醇"改为使用 "烯丙硫醇"， 且反应时间由 46h改为 48h， 其余同实施例 171。 最终得标题化合物 0.16g。  The "isopropyl thiol" in Example 171 was changed to use "allyl mercaptan", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.16 g.
TLC ¾=0·44(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 663 [M+H]+ ESI/MS: m/z 663 [M+H] +
实施例 201 Example 201
100  100
替换页 （细则第 26条) (2R，3S,4R,5R,8R,10R，l lR,12S，13S,14R)-l l-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己¾ ¾糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -13-(5-硫醇-戊基-硫基-甲基) -3，5，8,10,12,14-六甲基小氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下） Replacement page (Article 26) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D- 33⁄4 3⁄4 glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(5-thiol-pentyl-thio-methyl)-3,5,8, 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000102_0001
Figure imgf000102_0001
将实施例 171中的 "异丙硫醇"改为使用 " 1，5-戊二硫醇"， 且反应时间由 46h改为 48h， 其余同实施例 171。 最终得标题化合物 0.15g。  The "isopropyl thiol" in Example 171 was changed to use "1,5-pentanedithiol", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.15 g.
TLC ¾=0.44(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 725 [M+H]+ ESI/MS: m/z 725 [M+H] +
实施例 202 Example 202
N-{4- [(2R,3S，4R,5R，8R，10I lR，12S，13S，14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃 木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -15-酮 -1-氧-杂 -6-氮杂环十五垸 -13-基-甲基-硫基] -苯基 }-乙酰胺 （  N-{4-[(2R,3S,4R,5R,8R,10I lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)- β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one -1-oxo-hetero-6-azacyclopentadepin-13-yl-methyl-thio]-phenyl}-acetamide
Figure imgf000102_0002
Figure imgf000102_0002
将实施例 171中的 "异丙硫醇"改为使用 "4-乙酰氨基苯硫酚"， 且反应时间由 46h改 为 48h， 其余同实施例 171。 最终得标题化合物 0.16g。  The "isopropyl thiol" in Example 171 was changed to "4-acetamidothiophenol", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.16 g.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 756 [M+H]十  ESI/MS: m/z 756 [M+H] 十
实施例 203 Example 203
(21，38，411,51，811,1011，111，123,138，141 )-1 [[3，4，6-三脱氧-3-(二甲基氨基)- -0-己吡喃木糖基] 氧基] -2-乙基 -3，4,10，13-四羟基 -13-(6-硫醇-己基-硫基-甲基) -3，5，8,10，12，14-六甲基小氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下  (21,38,411,51,811,1011,111,123,138,141 )-1 [[3,4,6-Trideoxy-3-(dimethylamino)- -0-hexyranopyranosyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(6-thiol-hexyl-thio-methyl)-3,5,8,10,12,14- Hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000102_0003
Figure imgf000102_0003
将实施例 171中的 "异丙硫醇"改为使用 " 1,6-己二硫醇"， 且反应时间由 46h改为 48h， 其余同实施例 171。 最终得标题化合物 0.17g。  The "isopropyl thiol" in Example 171 was changed to use "1,6-hexanedithiol", and the reaction time was changed from 46h to 48h, and the rest were the same as in Example 171. The title compound was finally obtained in 0.17 g.
TLC R产 0.44(二氯甲烷： 甲醇 =5:1) 替换页 （细则第 26条) ESI/MS: mlz 739 [M+H]† TLC R yield 0.44 (dichloromethane: methanol = 5:1) Replacement page (Article 26) ESI/MS: mlz 739 [M+H] †
实施例 204 Example 204
(21 ,38,41 ,51^8 10¾111，128,138,141 )-11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3，4，10,13-四羟基 -13-(8-硫醇-庚基-硫基-甲基) -3,5，8，10，12,14-六甲基 -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见  (21,38,41 ,51^8 103⁄4111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyranosyl]oxy ]-2-Ethyl-3,4,10,13-tetrahydroxy-13-(8-thiol-heptyl-thio-methyl)-3,5,8,10,12,14-hexa Base-1-oxo-hetero-6-azacyclopentadecane-15-one (see structure formula)
Figure imgf000103_0001
Figure imgf000103_0001
将实施例 171中的 "异丙硫醇"改为使用 " 1,8-辛二硫醇" ， 且反应时间由 46h改为 3 天， 其余同实施例 171。 最终得标题化合物 0.16g。  The "isopropyl thiol" in Example 171 was changed to use "1,8-octanedithiol", and the reaction time was changed from 46h to 3 days, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.16 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5: 1)  TLC Rf = 0.44 (dichloromethane: methanol = 5: 1)
ESI/MS: m/z 767 [M+H]  ESI/MS: m/z 767 [M+H]
实施例 205 Example 205
(21，38，4 ，51 ,81，101 ,111，123，138,141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基)- -0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12，14-六甲基 -13- (吡啶 -2-基-硫基-甲基) -1-氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下）  (21,38,4,51,81,101,111,123,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)--0-hexyryl xylose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(pyridin-2-yl-thio- Methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000103_0002
Figure imgf000103_0002
将实施例 171中的 "异丙硫醇"改为使用 "2-巯基哌啶"， 且反应时间由 46h改为 3天， 其余同实施例 171。 最终得标题化合物 0.15g。  The "isopropyl thiol" in Example 171 was changed to use "2-mercaptopiperidine", and the reaction time was changed from 46h to 3 days, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.15 g.
TLC ¾=0.44(二氯甲烷： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 701 [M+H]十  ESI/MS: m/z 701 [M+H] 十
实施例 206 Example 206
(21 ,38，41 ,511,81，101，1111，128,135,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4，10，13-四羟基 -3,5，8，10,12，14-六甲基 -13- ( (壬基-硫基) -甲基) 小氧-杂 -6- 氮杂环十五浣 -15-酮 （结构式见下  (21,38,41,511,81,101,1111,128,135,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyranidyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-((indolyl-thio)-methyl Small oxygen-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000103_0003
Figure imgf000103_0003
将实施例 171中的 "异丙硫醇"改为使用 " 1-壬硫醇" , 且反应时间由 46h改为 3天， 替换页 （细则第 26条) 其余同实施例 171。 最终得标题化合物 0.4g。 The "isopropyl thiol" in Example 171 was changed to use "1-indolyl thiol", and the reaction time was changed from 46h to 3 days, replacing the page (Article 26) The rest are the same as in Example 171. The title compound was finally obtained in 0.4 g.
TLC R尸 0.44(二氯甲烷： 甲醇 =5:1)  TLC R corpse 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 749 [M+H]  ESI/MS: m/z 749 [M+H]
实施例 207 Example 207
(211,38,41 ,51 ,81 ,101 ,111 ,128，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基) 0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -13-((6-羟基 -己基 -硫)甲基) -3，5,8，10，12，14-六甲基 -1-氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下）  (211,38,41,51,81,101,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino) 0-hexyryl xylose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-((6-hydroxy-hexyl-thio)methyl)-3,5,8,10,12,14- Hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000104_0001
Figure imgf000104_0001
将实施例 171中的 "异丙硫醇"改为使用 "6-巯基-己 -1-醇"， 且反应时间由 46h改为 3 天， 其余同实施例 171。 最终得标题化合物 0.14g。  The "isopropyl thiol" in Example 171 was changed to use "6-mercapto-hexan-1-ol", and the reaction time was changed from 46h to 3 days, and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.14 g.
TLC Rf=0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 723 [M+H]  ESI/MS: m/z 723 [M+H]
实施例 208 Example 208
(21，38,4¾51^81^1011,11 ,128,138，141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基)- -0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12,14-六甲基 -13- (庚基-硫基-甲基）小氧-杂 -6-氮杂环 十五垸 -15-酮 （结构式见下）  (21,38,43⁄451^81^1011,11,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-o-hexanopyryl) Oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(heptyl-thio-methyl)oxygen -hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000104_0002
Figure imgf000104_0002
将实施例 171中的"异丙硫醇"改为使用" 1-庚硫醇"，且由" 60°C下反应 46h"改为" 65°C 下反应 58h" ， 其余同实施例 171。 最终得标题化合物 0.14g。  The "isopropyl thiol" in Example 171 was changed to use "1-heptanethiol", and was changed from "reaction 46 h at 60 ° C" to "reaction 58 h at 65 ° C", and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.14 g.
¾=0.44(二氯甲垸： 甲醇 =5:1)  3⁄4=0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 721 [M+H]  ESI/MS: m/z 721 [M+H]
实施例 2(^9 Example 2 (^9
(211,33，411，511，81 ,101 ,111，128,133,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8，10,12，14-六甲基 -13-(2-甲基-丁基-硫基-甲基) -1-氧-杂 -6- 氮杂环十五烷 -15-酮 （结构式见下）  (211, 33, 411, 511, 81, 101, 111, 128, 133, 141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyrranoxyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(2-methyl-butyl-thio -Methyl)-1-oxo-hetero-6-azabicyclopentadecane-15-one (see below for structural formula)
103 103
替换页 （细则第 26条)
Figure imgf000105_0001
Replacement page (Article 26)
Figure imgf000105_0001
将实施例 171中的 "异丙硫醇"改为使用 "2-甲基 -1-丁硫醇"， 且由 "60°C下反应 46h" 改为 "65°C下反应 58h"， 其余同实施例 171。 最终得标题化合物 0.13g。  The "isopropyl thiol" in Example 171 was changed to "2-methyl-1-butanethiol", and the reaction was changed from "46h at 60 °C" to "58h at 65 °C". Same as Example 171. The title compound was finally obtained in an amount of 0.13 g.
TLC RH).44(二氯甲垸： 甲醇 =5:1)  TLC RH).44 (dichloroformamidine: methanol = 5:1)
ES應 S: m/z 693 [M+H]+ ES should be S : m/z 693 [M+H] +
实施例 210 Example 210
(21 ,38,411，51 ,81 ,101，111 ,128，138，141^-13-(2，4-二氟-苯基-硫基-甲基)-11-[[3,4,6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10，13-四羟基 -3,5，8，10，12，14-六甲基小氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下）  (21,38,411,51,81,101,111,128,138,141^-13-(2,4-difluoro-phenyl-thio-methyl)-11-[[3,4,6- Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 ,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000105_0002
Figure imgf000105_0002
将实施例 171中的 "异丙硫醇"改为使用 "2，4-二氟苯硫酚" ， 且由 "6(TC下反应 46h" 改为 "65"C下反应 5天" ， 其余同实施例 171。 最终得标题化合物 0.22g。  The "isopropyl thiol" in Example 171 was changed to use "2,4-difluorothiophenol", and the reaction was changed from "6 (TC reaction 46h" to "65" C for 5 days", the rest The same as Example 171. The title compound (0.22 g) was obtained.
TLC Rf0.44(二氯甲垸： 甲醇 =5:1)  TLC Rf0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 735 [M+H]+ ESI/MS: m/z 735 [M+H] +
实施例 211 Example 211
(2R,3S，4R,5R，8I 0R，UR,12S，13S，14R)-1H[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -13- (吡啶 -2-基-甲基-硫基-甲基)小氧-杂 -6-氮杂环十五垸 -15-酮 （结构式见下）  (2R,3S,4R,5R,8I 0R,UR,12S,13S,14R)-1H[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyryl xylose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(pyridin-2-yl-methyl- Thio-methyl)oxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000105_0003
Figure imgf000105_0003
将实施例 171中的 "异丙硫醇"改为使用 "吡啶 -2-甲硫醇" ， 且由 "60'C下反应 46h" 改为 "65°C下反应 5天" ， 其余同实施例 171。 最终得标题化合物 0.14g。  The "isopropyl thiol" in Example 171 was changed to "pyridine-2-methyl thiol", and the reaction was changed from "60h C reaction 46h" to "65 °C reaction for 5 days", and the rest were carried out. Example 171. The title compound was finally obtained in an amount of 0.14 g.
TLC R产 0.44(二氯甲垸： 甲醇 =5:1)  TLC R yield 0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 714 [M+H]十  ESI/MS: m/z 714 [M+H] 十
实施例 212 Example 212
(2R,3S，4R,5R，8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D- Hexylpyranosyl]
104  104
替换页 （细则第 26条) 氧基] -13-(1，2-二甲基-丙基-硫基-甲基) -2-乙基 -3，4，10，13-四羟基 -3，5，8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮 （结构式见下 Replacement page (Article 26) Oxy]]13-(1,2-dimethyl-propyl-thio-methyl)-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 ,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000106_0001
Figure imgf000106_0001
将实施例 171中的 "异丙硫醇"改为使用 "3-甲基 -2-丁硫醇"， 且由 "60Ό下反应 46h" 改为 "65'C下反应 4天"， 其余同实施例 171。 最终得标题化合物 0.23g。  The "isopropyl thiol" in Example 171 was changed to use "3-methyl-2-butanethiol", and the "60 Ό reaction 46h" was changed to "65'C reaction for 4 days", the rest Example 171. The title compound was finally obtained in an amount of 0.23 g.
TLC Rt=0.44(二氯甲烷： 甲醇 =5:1)  TLC Rt = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 693 [M+H]十  ESI/MS: m/z 693 [M+H] 十
实施例 213 Example 213
(211，38,411551，81，101，1111?123，138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3，4,10，13-四羟基 -3，5，8，10，12，14-六甲基 -13-(1-甲基-丁基-硫基-甲基)小氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下） (211,38,411 5 51,81,101,1111 ? 123,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime- 0- hexyrranoxyl ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(1-methyl-butyl-thio -Methyl)oxy-hetero-6-azetidine, deca-decyl-15-one (see below for structural formula)
Figure imgf000106_0002
将实施例 171中的"异丙硫醇"改为使用" 2-戊硫醇"，且由" 60°C下反应 46h"改为" 65°C 下反应 4天" ， 其余同实施例 171。 最终得标题化合物 0.22g。
Figure imgf000106_0002
The "isopropyl thiol" in Example 171 was changed to "2-pentyl thiol", and was changed from "46h at 60 °C" to "4 days at 65 °C", and the rest of the same example 171 . The title compound was finally obtained in 0.22 g.
TLC Ri=0.44(二氯甲垸： 甲醇 =5:1)  TLC Ri=0.44 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z 693 [M+H]  ESI/MS: m/z 693 [M+H]
实施例 214 Example 214
(211，33，41 ,51，81，101，111，123,133,141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基)- -0-己吡喃木糖基] 氧基] -2-乙基 -13- (乙基-硫基-甲基） -3,4,10,13-四羟基 -3，5,8,10,12，14-六甲基小氧-杂 -6-氮杂环 十五浣 -15-酮 （结构式见下）  (211, 33, 41, 51, 81, 101, 111, 123, 133, 141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-o-hexanopyryl) Oxy]-2-ethyl-13-(ethyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy -hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000106_0003
Figure imgf000106_0003
将实施例 171中的"异丙硫醇"改为使用 "乙硫醇"，且由 "60°C下反应 46h"改为 "60'C 下反应 5天"， 其余同实施例 171。 最终得标题化合物 0.26g。  The "isopropyl thiol" in Example 171 was changed to use "ethanethiol", and was changed from "reaction at 60 ° C for 46 h" to "reaction at 60 ° C for 5 days", and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.26 g.
替换页 （细则第 26条) TLC Rf=0.44(二氯甲垸： 甲醇 =5:1) Replacement page (Article 26) TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 651M+H]十  ESI/MS: m/z 651M+H] ten
实施例 215 Example 215
(21 ,38，41 ,51，81，101，111 ,128,133，141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -13- ( (甲基-硫基） -甲基） -3，4，10,13-四羟基 -3，5，8,10,12，14-六甲基小氧-杂 -6- 氮杂环十五烷 -15-酮 （结构式见下）  (21,38,41,51,81,101,111,128,133,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-13-((methyl-thio)-methyl)-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyloxy-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000107_0001
Figure imgf000107_0001
将实施例 171中的 "异丙硫醇"改为使用 "甲硫醇"，且由 "60°C下反应 46h"改为 "65'C 下反应 4天"， 其余同实施例 171。 最终得标题化合物 0.26g。  The "isopropyl thiol" in Example 171 was changed to use "methyl mercaptan", and was changed from "reaction at 60 ° C for 46 h" to "reaction at 65 ° C for 4 days", and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.26 g.
Ri=0.40(二氯甲垸： 甲醇 =5:1)  Ri = 0.40 (dichloromethane: methanol = 5:1)
ESI/MS: m/z 637 [M+H]  ESI/MS: m/z 637 [M+H]
实施例 216 Example 216
(2R,3S,4R,5R，8R,10R,llR，12S，13S，14R)-l l-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -3，4，10,13-四羟基 -3,5,8,10,12,14-六甲基 -13-((0-甲苯-硫基) -甲基 )-1-氧-杂 -6-氮杂 环十五垸 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,llR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-((0-toluene- Thio)-methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000107_0002
Figure imgf000107_0002
将实施例 171中的 "异丙硫醇"改为使用 "2-甲基苯硫酚"， 且由 "60°C下反应 46h"改 为 "60°C下反应 4天"， 其余同实施例 171。 最终得标题化合物 0.16g。  The "isopropyl thiol" in Example 171 was changed to "2-methyl thiophenol", and the "reaction at 60 ° C for 46 h" was changed to "reaction at 60 ° C for 4 days", and the rest were carried out. Example 171. The title compound was finally obtained in an amount of 0.16 g.
TLC ¾=0.44(二氯甲垸： 甲醇 =5:1)  TLC 3⁄4 = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z713 [M+H]  ESI/MS: m/z713 [M+H]
实施例 217 Example 217
(21，33，41 ,51 ,811,10 ,1111,128，138,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -3,4,10,13-四羟基 -13-(4-硫醇-戊基-硫基-甲基) -3，5,8，10，12,14-六甲基 -1-氧-杂 -6- 氮杂环十五垸 -15-酮 （结枸式见下  (21,33,41,51,811,10,1111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(4-thiol-pentyl-thio-methyl) -3,5,8,10,12 ,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one (see knot
Figure imgf000107_0003
Figure imgf000107_0003
替换页 （细则第 26条) 将实施例 171中的 "异丙硫醇"改为使用 "14-丁二硫醇"， 且由 "60°C下反应 46h"改 为 "60°C下反应 4天" 其余同实施例 171。 最终得标题化合物 0.14g Replacement page (Article 26) The "isopropyl thiol" in Example 171 was changed to "14-butanedithiol", and the "reaction at 60 ° C for 46 h" was changed to "reaction at 60 ° C for 4 days". . The title compound was finally obtained.
TLC RH).42(二氯甲烷： 甲醇 =5:1)  TLC RH).42 (dichloromethane: methanol = 5:1)
ESI/MS: m/z712 [M+H]+ ESI/MS: m/z712 [M+H] +
实施例 218 Example 218
(2R3S,4R,5R,8R10R,llR,12S,13S14R)-ll-[[34,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -13-(34-二氟-苯基-硫基-甲基) -34,1013-四羟基 -358,1012,14-六甲基小氧-杂 -6- 氮杂环十五垸 -15-酮 （结构式见下  (2R3S,4R,5R,8R10R,llR,12S,13S14R)-ll-[[34,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy] -2-ethyl-13-(34-difluoro-phenyl-thio-methyl)-34,1013-tetrahydroxy-358,1012,14-hexamethyloxy-hetero-6-azacyclocycle Fifteen 垸-15-ketone (see below for structural formula)
Figure imgf000108_0001
将实施例 171中的 异丙硫醇"改为使用 "3,4-二氟苯硫酚"， 且由 "60'C下反应 46h" 改为 "60'C下反应 4天"， 其余同实施例 171。 最终得标题化合物 0.13g
Figure imgf000108_0001
Change the isopropyl mercaptan in Example 171 to "3,4-difluorothiophenol", and change from "60h C reaction 46h" to "60'C reaction for 4 days", the rest Example 171. The title compound was finally obtained.
TLC Rf=0.43(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.43 (dichloromethane: methanol = 5:1)
ESI/MS: m/z735 [M+H]  ESI/MS: m/z735 [M+H]
实施例 219 Example 219
(21 3841^51 81,101?111,128138,141)-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -13-(3-氟-苯基-硫基-甲基) -3410,13-四羟基 -35,8,10,12,14-六甲基 -1-氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下） (21 3841^51 81,101 ? 111,128138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-l-hexyranosyl]oxy] -2-ethyl-13-(3-fluoro-phenyl-thio-methyl)-3410,13-tetrahydroxy-35,8,10,12,14-hexamethyl-1-oxo-hetero- 6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000108_0002
Figure imgf000108_0002
将实施例 171中的 "异丙硫醇"改为使用 "间氟苯硫酚" ， 且由 "60Ό下反应 46h"改 为 "60Ό下反应 4天" ， 其余同实施例 171。 最终得标题化合物 0.14g  The "isopropyl thiol" in Example 171 was changed to "m-fluorothiophenol", and the "60 Ό reaction 46h" was changed to "60 Ό reaction for 4 days", and the rest were the same as in Example 171. The title compound was finally obtained.
TLC Rf=0.44(二氯甲烷： 甲醇 =5:1) TLC Rf = 0.44 (dichloromethane: methanol = 5:1)
ESI/MS: m/z718 [M+H]  ESI/MS: m/z718 [M+H]
实施例 220 Example 220
(21^38,4^511811,101 1111,128,138141)-11-[[3,46-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木糖基] 氧基] -2-乙基 -13-(4-氟-苄基-硫基-甲基) -3410,13-四羟基 -3,5,8,1012,14-六甲基小氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下）  (21^38,4^511811,101 1111,128,138141)-11-[[3,46-Trideoxy-3-(dimethylamino)-indole-0-hexylopyranosyl]oxy ]-2-Ethyl-13-(4-fluoro-benzyl-thio-methyl)-3410,13-tetrahydroxy-3,5,8,1012,14-hexamethyloxy-hetero-6 -azacyclopentadecane-15-one (see below for structural formula)
107 107
替换页 （细则第 26条)
Figure imgf000109_0001
Replacement page (Article 26)
Figure imgf000109_0001
将实施例 171中的 "异丙硫醇"改为使用 "对氟苯甲硫醇" ， 且由 "60'C下反应 46h" 改为 "6CTC下反应 3天" ， 其余同实施例 171。 最终得标题化合物 0.1 lg。  The "isopropyl thiol" in Example 171 was changed to "p-fluorobenzothiol", and the reaction at "60'C for 46h" was changed to "6CTC for 3 days", and the rest were the same as in Example 171. The title compound was finally obtained as 0.1 lg.
TLC RfH).45(二氯甲垸： 甲醇 =5:1)  TLC RfH).45 (dichloroformamidine: methanol = 5:1)
ESI/MS: m/z731 [M+H]†。 ESI/MS: m/z 731 [M+H] † .
实施例 2?1 Example 2?1
(2R，3S，4R，5R，8R,10R,l lR,12S,13S,14R)-ll-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基] 氧基] -2-乙基 -13-(2-氟-苄基-硫基-甲基) -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮 杂环十五垸 -15-酮 （结构式见下）  (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-ll-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-13-(2-fluoro-benzyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8,10 ,12,14-hexamethyloxy-hetero-6-nitrohecyclopentadecane-15-one (see below for structural formula)
Figure imgf000109_0002
Figure imgf000109_0002
将实施例 171中的 "异丙硫醇"改为使用 "2-氟苯甲硫醇"， 且由 "60°C下反应 46h"改 为 "65°C下反应 4天" ， 其余同实施例 171。 最终得标题化合物 0.13g。  The "isopropyl thiol" in Example 171 was changed to "2-fluorobenzyl mercaptan", and the "reaction at 60 ° C for 46 h" was changed to "reaction at 65 ° C for 4 days", and the rest were carried out. Example 171. The title compound was finally obtained in an amount of 0.13 g.
TLC Rf=0.46(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.46 (dichloromethane: methanol = 5:1)
ESI/MS: m/z731 [M+H]+。  ESI/MS: m/z 731 [M+H]+.
实施例 222 Example 222
(21，38，41^51，81 ,10¾11¾128，138,141 )-13-(4-氯-苄基-硫基-甲基) -11-[ (4-二甲基氨基 -3-羟基 -6-甲基 -P-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮 杂环十五烷 -15-酮 （结构式见下）  (21,38,41^51,81,103⁄4113⁄4128,138,141)-13-(4-chloro-benzyl-thio-methyl)-11-[(4-dimethylamino-3-hydroxy-6- Methyl-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy- Hetero-6-azacyclopentadecane-15-one (see below for structural formula)
Figure imgf000109_0003
Figure imgf000109_0003
将实施例 171中的 "异丙硫醇"改为使用 "对氯苯甲硫醇" ， 且由 "60'C下反应 46h" 改为 "65Ό下反应 4天"， 其余同实施例 171。 最终得标题化合物 0.15g。  The "isopropyl thiol" in Example 171 was changed to "p-chlorobenzothiol", and the reaction at "60'C for 46h" was changed to "65 Ό under reaction for 4 days", and the rest were the same as in Example 171. The title compound was finally obtained in an amount of 0.15 g.
TLC Rf=0.47(二氯甲烷： 甲醇 =5:1)  TLC Rf = 0.47 (dichloromethane: methanol = 5:1)
ESI/MS: m/z747 [M+H]十。  ESI/MS: m/z 747 [M+H] ten.
实施例 22 Example 22
本发明的实施例制备化合物的药理活性研究 替换页 （细则第 26条) 按照美国 NCCLS抗微生物药物敏感性实验操作标准对制备的实施 6至实施例 222制备化 合物进行抗菌活性测定， 本操作采用微量肉汤稀释法测定实施例制备的药物对下列实验菌株 的 MIC。 Illustrative of the pharmacological activity of the compounds prepared in the examples of the present invention (Article 26) The prepared compounds of Examples 6 to 222 were tested for antibacterial activity according to the NCCLS Antimicrobial Susceptibility Test Protocol of the United States. The MIC of the drug prepared in the examples was determined by the micro-broth dilution method for the following experimental strains.
(1)培养基及配制方法： MHB琼脂培养基、 MHB肉汤培养基， 均购自北京奥博星生物技 术有限公司。 使用前按说明书要求进行配制， 链球菌培养在培养基灭菌后温度降至 60Ό以下 时加入 10%的小牛血清。  (1) Medium and preparation method: MHB agar medium and MHB broth medium were purchased from Beijing Aoboxing Biotechnology Co., Ltd. Prepare according to the instructions before use. Streptococci culture is added with 10% calf serum when the temperature of the medium is reduced to less than 60Ό.
(2)试验菌株： 金黄色葡萄球菌标准菌株 ATCC 25923、 溶血性链球菌标准菌株 C55100、 化脓链球菌标准菌株 CMCC (B) 32210、 表皮葡萄球菌标准菌株 ATCC12228、 大肠杆菌标 准菌株 C83921、胸膜肺炎放线杆菌标准菌株 M62，购自中华人民共和国***临床检测中心。  (2) Test strain: Staphylococcus aureus standard strain ATCC 25923, hemolytic streptococcus standard strain C55100, S. pyogenes standard strain CMCC (B) 32210, Staphylococcus epidermidis standard strain ATCC12228, Escherichia coli standard strain C83921, pleuropneumonia The standard strain M62 of the bacillus was purchased from the Clinical Testing Center of the Ministry of Health of the People's Republic of China.
(3)试验药物： 本发明实施例 6到实施例 222所制备的化合物； 对照药物： 阿奇霉素（中 国药品生物制品检定所， 批号为 130352— 200405) ， 克拉霉素（浙江八达通化工信息公司， 经测定含量为 96.7%) 。  (3) Test drug: The compound prepared in Example 6 to Example 222 of the present invention; Control drug: Azithromycin (China National Institute for the Control of Pharmaceutical and Biological Products, batch number 130352-200405), clarithromycin (Zhejiang Octopus Chemical Information Co., Ltd., The measured content was 96.7%).
(4)试验方法：用 10%的乙醇为溶剂将药物溶解，用蒸馏水补足到所需体积并充分混匀后， 配制成浓度为 2048 g/mL的溶液， 备用。 超净工作台中 96孔板微量培养板中加入灭菌好的 肉汤 100μί， 将配制好的各药物加入第 1、 3、 5、 7、 11列的第 1孔， 二倍稀释法稀释至第 8 孔， 继续稀释至下一列第 1-7孔， 第 8排不加药物作为生长对照， 各孔加稀释好的浓度为 105 个 /mL的菌液 ΙΟΟμί, 此时， 药物浓度分别为 512、 256、 128、 64、 32、 16、 8、 4、 2、 1、 0.5、 0.25、 0.125、 0.0625、 0.03125 g/ml。 微量振荡器振摇均匀， 37°C孵育 24小时， 观察结果， 无菌生长的最低浓度为该药的 MIC。 (4) Test method: Dissolve the drug with 10% ethanol as a solvent, make up the required volume with distilled water and mix well, and prepare a solution with a concentration of 2048 g/mL, and set aside. Add 100 μί of sterilized broth to the 96-well plate microplate in the clean bench. Add the prepared drugs to the first well of columns 1, 3, 5, 7, and 11. Dilute to the first dilution. 8 wells, continue to dilute to the next column 1-7, the eighth row without drugs as a growth control, each well added diluted concentration of 10 5 / mL of bacteria ΙΟΟμί, at this time, the drug concentration was 512 , 256, 128, 64, 32, 16, 8, 4, 1, 1, 0.5, 0.25, 0.125, 0.0625, 0.03125 g/ml. The micro-oscillator was shaken evenly and incubated at 37 ° C for 24 hours. The results showed that the lowest concentration for aseptic growth was the MIC of the drug.
(5)测定结果： 实施例 6至实施例 222制备的通式化合物和两种对照药物对 6株细菌的 MIC值测定结果见表 1， 其中 MIC单位为 g/mL。  (5) Measurement results: The MIC values of the six types of bacteria prepared by the compound of the formula prepared in Example 6 to Example 222 and the two control drugs are shown in Table 1, wherein the MIC unit is g/mL.
表 1  Table 1
Figure imgf000110_0001
Figure imgf000110_0001
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1 U 1 U
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实施例 218 0.25 2 4 0.5 64 128 实施例 219 0.5 2 2 2 8 16 实施例 220 0.5 2 2 1 32 16 实施例 221 0.25 2 1 0.5 - 64 实施例 222 0.25 4 4 2 64 128 注： "-"表示 MIC大于 256 g mL  Example 218 0.25 2 4 0.5 64 128 Example 219 0.5 2 2 2 8 16 Example 220 0.5 2 2 1 32 16 Example 221 0.25 2 1 0.5 - 64 Example 222 0.25 4 4 2 64 128 Note: "-" Indicates MIC greater than 256 g mL
从表 1可以看出本发明制备例得到的化合物大部分对标准菌株具有体外抗菌活性， 并且 有一部分化合物的活性与对照药相比， 明显优于对照药的体外抗菌活性。  It can be seen from Table 1 that most of the compounds obtained in the preparation examples of the present invention have in vitro antibacterial activity against standard strains, and some of the compounds have significantly superior in vitro antibacterial activity to the control drugs as compared with the control drugs.
实施例 224 Example 224
本发明的实施例制备化合物对耐药菌的药理活性研究  Study on Pharmacological Activity of Compounds Prepared against Drug-Resistant Bacteria in Examples of the Invention
为了进一步验证实施例化合物的抗菌活性， 通过标准菌株体外活性测定， 筛选出对标准 菌株抗菌活性强的化合物， 对耐药金黄色葡萄球菌和耐药肺炎链球菌进行了敏感性测定。  In order to further verify the antibacterial activity of the compounds of the examples, the compounds having strong antibacterial activity against the standard strains were screened by in vitro activity assay of the standard strains, and the sensitivity of the resistant Staphylococcus aureus and the resistant Streptococcus pneumoniae was determined.
测定菌株： 红霉素耐药金黄色葡萄球菌 （MSSA-EAR) 、 耐药肺炎链球菌： MLSB型耐 药肺炎链球菌 Bl(S.pneumoniae(ermB))、 M型耐药肺炎链球菌 A22072(S.pneumoniae(mefA)) 和 MLSB+M型耐药肺炎链球菌 S.pneumoniae(ermB+mefA)) (北京协和医科大学)。 以上菌株在 山东大学硕士论文"抗耐药菌十五元大环内酯衍生物的设计、 合成及抗菌活性研究 "中公开。 Determination of strains: erythromycin-resistant Staphylococcus aureus (MSSA-EAR), drug-resistant Streptococcus pneumoniae: MLS type B -resistant Streptococcus pneumoniae (S.pneumoniae (ermB)), M-type resistant Streptococcus pneumoniae A22072 (S.pneumoniae (mefA)) and MLS B + M-type resistant Streptococcus pneumoniae S. pneumoniae (ermB+mefA) (Beijing Union Medical University). The above strains are disclosed in the master's thesis "Study on the design, synthesis and antibacterial activity of fifteen-membered macrolide derivatives of drug-resistant bacteria".
测定方法:采用试管二倍稀释法测定化合物对红霉素耐药金黄色葡萄球菌 (MSSA-EAR)、 和上述耐药肺炎链球菌的体外抗菌活性。 对照药物： 阿奇霉素 （中国药品生物制品检定所， 批号为 130352— 200405 ) ， 克拉霉素 （浙江八达通化工信息公司， 经测定含量为 96.7%) 。 测定结果见表 2。  Assay method: The in vitro antibacterial activity of the compound against erythromycin-resistant Staphylococcus aureus (MSSA-EAR) and the above-mentioned drug-resistant S. pneumoniae was determined by a two-fold dilution test. Control drug: Azithromycin (China National Institute for the Control of Pharmaceutical and Biological Products, batch number 130352—200405), clarithromycin (Zhejiang Octopus Chemical Information Company, the measured content was 96.7%). The measurement results are shown in Table 2.
表 2 Table 2
Figure imgf000116_0001
Figure imgf000116_0001
1 15  1 15
替换页 （细则第 26条) 实施例 43 4 0.5 8 2 实施例 45 2 0.25 32 1 实施例 6 4 0.25 4 2 实施例 47 1 0.25 16 1 实施例 48 1 0.125 64 1 实施例 50 2 0.5 64 2 实施例 51 2 0.25 16 2 实施例 52 2 0.5 16 2 实施例 53 2 0.25 64 2 实施例 54 2 0.5 32 2 实施例 55 1 0.25 32 1 实施例 56 1 0.5 8 2 实施例 58 2 0.5 64 1 实施例 59 2 0.125 64 2 实施例 60 2 0.125 32 2 实施例 63 1 0.5 8 2 实施例 66 1 0.25 32 1 实施例 67 1 0.25 64 1 实施例 68 4 0.25 64 2 实施例 71 2 0.5 64 1 实施例 77 1 0.5 16 1 实施例 79 1 0.25 2 1 实施例 80 4 0.25 8 2 实施例 81 4 0.5 32 2 实施例 89 4 0.125 32 1 实施例 91 2 0.125 32 1 实施例 94 2 0.25 16 1 实施例 96 2 0.125 4 1 实施例 99 4 0.125 8 2 实施例 103 1 0.125 32 1 实施例 106 1 0.125 32 2 实施例 110 4 2 4 1 实施例 111 2 1 4 1 实施例 112 1 1 8 2 实施例 113 2 1 32 2 实施例 114 2 1 4 2 实施例 115 2 2 8 2 实施例 116 4 0.5 4 1 实施例 Π9 4 0.25 8 2 实施例 124 1 0.125 32 0.5 Replacement page (Article 26) Example 43 4 0.5 8 2 Example 45 2 0.25 32 1 Example 6 4 0.25 4 2 Example 47 1 0.25 16 1 Example 48 1 0.125 64 1 Example 50 2 0.5 64 2 Example 51 2 0.25 16 2 Implementation Example 52 2 0.5 16 2 Example 53 2 0.25 64 2 Example 54 2 0.5 32 2 Example 55 1 0.25 32 1 Example 56 1 0.5 8 2 Example 58 2 0.5 64 1 Example 59 2 0.125 64 2 Example 60 2 0.125 32 2 Example 63 1 0.5 8 2 Example 66 1 0.25 32 1 Example 67 1 0.25 64 1 Example 68 4 0.25 64 2 Example 71 2 0.5 64 1 Example 77 1 0.5 16 1 Example 79 1 0.25 2 1 Example 80 4 0.25 8 2 Example 81 4 0.5 32 2 Example 89 4 0.125 32 1 Example 91 2 0.125 32 1 Example 94 2 0.25 16 1 Example 96 2 0.125 4 1 Example 99 4 0.125 8 2 Example 103 1 0.125 32 1 Example 106 1 0.125 32 2 Example 110 4 2 4 1 Example 111 2 1 4 1 Example 112 1 1 8 2 Example 113 2 1 32 2 Example 114 2 1 4 2 Example 115 2 2 8 2 Example 116 4 0.5 4 1 Example Π 9 4 0.25 8 2 Example 124 1 0.125 32 0.5
116  116
替换页 （细则第 26条) 实施例 126 2 0.5 64 2 Replacement page (Article 26) Example 126 2 0.5 64 2
实施例 127 4 0.125 16 1 Example 127 4 0.125 16 1
实施例 128 4 0.5 2 2 Example 128 4 0.5 2 2
实施例 129 2 0.25 32 8 Example 129 2 0.25 32 8
实施例 131 4 0.25 4 1 Example 131 4 0.25 4 1
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实施例 136 2 0.125 32 2 Example 136 2 0.125 32 2
实施例 139 4 0.5 32 2 Example 139 4 0.5 32 2
实施例 140 4 0.25 32 2 Example 140 4 0.25 32 2
实施例 142 4 0.5 64 4 Example 142 4 0.5 64 4
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实施例 159 1 0.125 8 1 Example 159 1 0.125 8 1
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实施例 178 1 0.5 2 0.5 实施例 180 2 0.125 4 2 Example 178 1 0.5 2 0.5 Example 180 2 0.125 4 2
实施例 181 2 0.5 16 1 Example 181 2 0.5 16 1
实施例 186 2 0.125 4 1 Example 186 2 0.125 4 1
实施例 187 1 0.25 16 2 Example 187 1 0.25 16 2
实施例 191 2 0.125 8 2 Example 191 2 0.125 8 2
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实施例 218 2 0.25 64 1 Example 218 2 0.25 64 1
实施例 219 8 0.5 4 2 Example 219 8 0.5 4 2
实施例 220 4 0.5 8 1 Example 220 4 0.5 8 1
实施例 221 4 0.125 4 2 Example 221 4 0.125 4 2
实施例 222 4 0.25 16 2 Example 222 4 0.25 16 2
可以得出： 受测实施例化合物对耐药菌大部分有很好的体外活性。 与对照药 It can be concluded that the test example compounds have good in vitro activity against most of the resistant bacteria. And comparator
117  117
替换页 （细则第 26条) 物相比表现出明显的抗耐药菌活性。 从各化合物活性平均水平看， 化合物抗菌活性明显。 对 M型耐药肺炎链球菌 A22072的实施例 26、 31、 48、 59、 60、 89、 91、 96、 99、 103、 106、 124、 127、 136、 155、 159、 168、 175、 180、 186、 191、 196、 197、 210、 212, 213、 221的药物 MIC为 0.125 g/mL。 抗菌活性为对照药阿奇霉素和克拉霉素的 32倍。 Replacement page (Article 26) Compared with the substance, it showed obvious anti-resistant bacteria activity. From the average level of activity of each compound, the antibacterial activity of the compound was remarkable. Examples 26, 31, 48, 59, 60, 89, 91, 96, 99, 103, 106, 124, 127, 136, 155, 159, 168, 175, 180 of the M-type resistant Streptococcus pneumoniae A22072, The drug MIC of 186, 191, 196, 197, 210, 212, 213, 221 was 0.125 g/mL. The antibacterial activity was 32 times that of the control drugs azithromycin and clarithromycin.
实施例 2 5  Example 2 5
本发明的实施例制备的化合物对肺炎球菌小鼠存活率的影响  Effect of compounds prepared in the examples of the present invention on the survival rate of pneumococcal mice
实施例制备化合物在体内的抗菌活性使用本领域技术人员熟知的常规动物实验方法 进行检测， 实验动物为 BALB/c小鼠。  EXAMPLES The antibacterial activity of the compounds prepared in vivo was tested using conventional animal experiments well known to those skilled in the art, and the experimental animals were BALB/c mice.
( 1 )试验材料： 肺炎链球菌标准菌株， 编号为 CMCC 31203 , 购于中国医学细菌保 藏管理中心。 阿奇霉素， 购自中国药品生物制品鉴定所， 批号为 130352— 200405。  (1) Test material: The standard strain of Streptococcus pneumoniae, numbered CMCC 31203, was purchased from the China Medical Bacterial Collection Management Center. Azithromycin, purchased from China National Institute for the Control of Pharmaceutical and Biological Products, batch number 130352—200405.
试验药物： 本发明实施例 26、 3 48、 59、 60、 89、 91、 96、 99、 103、 106、 124、 127、 136、 155、 159、 168、 175、 180、 186、 191、 196、 197、 210、 212、 213、 221 制 备所得的化合物， 同时用阿奇霉素 （中国药品生物制品检定所， 批号为 130352— 200405 ) 进行对照。 实验前用无水乙醇将药物溶解， 用蒸馏水补足到所需体积并混匀后无菌过滤， 配 制成浓度为 lmg/mL的液体。  Test Drugs: Inventive Examples 26, 3 48, 59, 60, 89, 91, 96, 99, 103, 106, 124, 127, 136, 155, 159, 168, 175, 180, 186, 191, 196, 197, 210, 212, 213, 221 The obtained compound was prepared and compared with azithromycin (China National Institute for the Control of Pharmaceutical and Biological Products, batch number 130352-200405). The drug was dissolved in absolute ethanol before the experiment, and the volume was made up with distilled water and mixed, and then aseptically filtered to prepare a liquid having a concentration of 1 mg/mL.
( 2 )试验方法： 5-6周的小鼠 350只， 挑选体重在 18-20g之间的进行分笼， 每笼 10 只， 饲养 72h， 观察正常可进入试验。 实验前将肺炎链球菌用血平板培养 24h, 加入含血 清的无菌肉汤中 37°C振荡培养（120r/min) 20h增菌培养， 进行活菌计数。用灭菌生理盐 水稀释至 5x l08cfu/mL， 小鼠腹腔注射进行攻毒， 每只 0.5mL。 攻毒第 2天， 取上述实施 例制备的化合物以及对照药物， 按 5mg/kg体重颈部皮下注射进行给药， 连续给药 3天， 同时设空白对照组合药物对照组， 药物对照组攻毒后不给药， 药物对照组按 10mg kg体 重注射阿奇霉素， 攻毒、 给药后， 每天观察动物， 记录各组的死亡数， 观察至第 7天。 (2) Test method: 350 mice of 5-6 weeks were selected, and the weight was selected between 18-20g, and 10 cages per cage were kept for 72 hours. Normal admission test was observed. Before the experiment, S. pneumoniae was cultured for 24 hours, and added to serum-containing sterile broth to incubate at 37 ° C for 20 h to enhance the bacterial count. Dilute to 5×10 8 cfu/mL with sterile saline, and the mice were intraperitoneally injected for challenge, 0.5 mL each. On the 2nd day of the challenge, the compound prepared in the above examples and the control drug were administered subcutaneously in the neck of 5 mg/kg body weight for 3 days, and the blank control combination drug control group and the drug control group were challenged. After the administration, the drug control group was injected with azithromycin at 10 mg kg body weight. After challenge and administration, the animals were observed every day, and the number of deaths in each group was recorded, and the day 7 was observed.
( 3 ) 试验结果见表 3 , 表 3为本发明通式化合物对肺炎球菌小鼠存活率的影响。  (3) The test results are shown in Table 3, and Table 3 shows the effect of the compound of the present invention on the survival rate of pneumococcal mice.
表 3  table 3
Figure imgf000119_0001
Figure imgf000119_0001
1 18  1 18
替换页 （细则第 26条) 从表 3可以看出， 通过对本发明实施例制备化合物中的 30个化合物进行体内抗菌活 性测定，结果表明按 5mg/kg体重给予本发明结构式的化合物能降低肺炎球菌引起的小鼠 感染死亡， 与对照组相比， 能够明显提高攻毒后试验组小鼠的存活率， 表现出明显的体 内抗菌活性。 Replacement page (Article 26) As can be seen from Table 3, by performing in vivo antibacterial activity assay on 30 compounds in the compounds prepared in the examples of the present invention, it was found that administration of the compound of the formula of the present invention at 5 mg/kg body weight can reduce the death of mice infected by pneumococcal infection, and Compared with the control group, the survival rate of the mice in the test group after the challenge was significantly improved, and the in vivo antibacterial activity was exhibited.
以上所述仅为本发明的较佳实施例而已， 并不用以限制本发明， 凡在本发明的精神 和原则之内， 所作的任何修改、 等同替换、 改进等， 均应包含在本发明的保护范围之内。  The above is only the preferred embodiment of the present invention, and is not intended to limit the present invention. Any modifications, equivalents, improvements, etc., which are included in the spirit and scope of the present invention, should be included in the present invention. Within the scope of protection.
119 119
替换页 （细则第 26条)  Replacement page (Article 26)

Claims

权利要求书 Claim
1. 一种具有如下通 )所示的化合物:  1. A compound having the following:
Figure imgf000121_0001
Figure imgf000121_0001
( I )  (I)
其中， 是11， 羟基或甲氧基； R2是羟基； 1 3是以杂原子取代或未取代的有机物， 且所述杂原子为卤素、 N、 0和 S中的一种或多种； R4是 H、 苄氧羰基、 苯甲酰基或乙 酰基。 Wherein, is 11, a hydroxyl group or a methoxy group; R 2 is a hydroxyl group; 13 is an organic substance substituted or unsubstituted with a hetero atom, and the hetero atom is one or more of halogen, N, 0 and S; R4 is H, benzyloxycarbonyl, benzoyl or acetyl.
2. 根据权利要求 1所述的化合物， 其特征在于， R3为 -CH2R2Q， 其中 R2fl为含 C、 H、 0、 N、 S和卤素中至少一种原子的有机或无机基团。 The compound according to claim 1, wherein R 3 is -CH 2 R 2Q , wherein R 2fl is an organic or inorganic group containing at least one of C, H, 0, N, S and halogen group.
3. 根据权利要求 1或 2所述的化合物， 其特征在于， R3为 -CH2NHR3Q， 其中 R30为 含0、 H、 0、 N、 S和卤素中至少一种原子的有机或无机基团。 The compound according to claim 1 or 2, wherein R 3 is -CH 2 NHR 3Q , wherein R 30 is an organic group containing at least one of 0, H, 0, N, S and halogen Inorganic group.
4. 根据权利要求 3所述的化合物， 其特征在于， R3()选自 H， 氨基， 甲基， 乙基， 烯丙基， 正丁基， 异丁基， 2-甲氧乙基， 环戊基， 3-甲氧丙基， 3-乙氧丙基， 正丙基， 异 丙基， 2-羟基乙基， 环丙基， 2,2，2-三氟乙基， 2-丙炔基， 仲丁基， 叔丁基， 正己基， 乙 烯基， 乙炔基， 1-甲基小丙烯基， 3-甲氧基小丙炔基， 3-二甲基氨基小丙炔基， 3-羟基 -1-丙炔基， 3-羟基 -1-丙烯基， 3-羟丙基， 3-甲氧基 -1-丙烯基， 3-甲氧基丙基， 1-丙炔基， 叠氮基甲基， 甲酰基甲基， 6-氰基 -1-戊炔基， 3-二甲基氨基 -1-丙烯基， 或 3-二甲基氨基 丙基。 The compound according to claim 3, wherein R 3 () is selected from the group consisting of H, amino, methyl, ethyl, allyl, n-butyl, isobutyl, 2-methoxyethyl, Cyclopentyl, 3-methoxypropyl, 3-ethoxypropyl, n-propyl, isopropyl, 2-hydroxyethyl, cyclopropyl, 2,2,2-trifluoroethyl, 2-propane Alkynyl, sec-butyl, tert-butyl, n-hexyl, vinyl, ethynyl, 1-methylpropenyl, 3-methoxypropynyl, 3-dimethylaminopropynyl, 3 -hydroxy-1-propynyl, 3-hydroxy-1-propenyl, 3-hydroxypropyl, 3-methoxy-1-propenyl, 3-methoxypropyl, 1-propynyl, stack Nitromethyl, formylmethyl, 6-cyano-1-pentynyl, 3-dimethylamino-1-propenyl, or 3-dimethylaminopropyl.
5. 根据权利要求 3 所述的化合物， 其特征在于， 为 -CH2NH-(CH2)mR4o, 其中 m 是 1-4的整数， R40为含 C、 H、 0、 N、 S和卤素中至少一种原子的有机或无机基团。 The compound according to claim 3, which is -CH 2 NH-(CH 2 ) m R4o, wherein m is an integer of 1-4, and R40 is C, H, 0, N, S and An organic or inorganic group of at least one atom in the halogen.
6. 根据权利要求 5所述的化合物， 其特征在于， R40选自 H， 含有或不含有杂原子 的有机基团， 所述杂原子为卤素、 N、 0或8。  The compound according to claim 5, wherein R40 is selected from the group consisting of H, an organic group having or not containing a hetero atom, and the hetero atom is halogen, N, 0 or 8.
7. 根据权利要求 6所述的化合物，其特征在于， R4Q选自含有或不含有杂原子的 d-C 垸基， -C6垸氧基， C2-C6链烯基， C2-C6炔基， 和 5-20元芳基或杂芳基， 且前述基团 可任选地连接有含碳的取代基团。 The compound according to claim 6, wherein R 4 Q is selected from dC fluorenyl group having or not containing a hetero atom, -C 6 decyloxy group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl, and 5-20 membered aryl or heteroaryl, and the aforementioned group may be optionally bonded to a carbon-containing substituent.
8. 根据权利要求 5所述的化合物，其特征在于， R40为含有或不含有取代基的 C6-C10 芳基或 C5-C2()的杂芳基， 所述杂芳基中杂原子为卤素、 N、 0或8。 The compound according to claim 5, wherein R40 is a C 6 -C 10 aryl group or a C 5 -C 2 () heteroaryl group having or not having a substituent, wherein the heteroaryl group is The hetero atom is halogen, N, 0 or 8.
9. 根据权利要求 1或 2所述的化合物， 其特征在于， R3为 -CH2SR5Q， 其中 R5。为以 杂原子取代或未取代的有机物， 所述杂原子为卤素、 N、 0或8。 The compound according to claim 1 or 2, wherein R 3 is -CH 2 SR 5Q , wherein R 5 is . In the case of an organic substance substituted or unsubstituted with a hetero atom, the hetero atom is halogen, N, 0 or 8.
10. 根据权利要求 9所述的化合物， 其特征在于， 其中 R5Q为选自含有或不含有杂原 The compound according to claim 9, wherein R 5Q is selected from the group consisting of containing or not containing impurities
120  120
替换页 （细则第 26条) 子的 - o烷基， d-C6烷氧基， C2-C6链烯基， C2-C6炔基， 和 5-20元芳基或杂芳基， 且前述基团可任选地连接有含碳的取代基团。 Replacement page (Article 26) -Oalkyl, dC 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and 5-20 membered aryl or heteroaryl, and the aforementioned groups are optionally A carbon-containing substituent group is attached.
11. 根据权利要求 10所述的化合物， 其特征在于， 其中 R5o为甲基， 乙基， 烯丙基， 正丁基， 异丁基， 2-甲氧乙基， 环戊基， 3-甲氧丙基， 3-乙氧丙基， 正丙基， 异丙基， 2- 羟基乙基， 环丙基， 仲丁基， 叔丁基， 或正已基。 The compound according to claim 10, wherein R 5 o is methyl, ethyl, allyl, n-butyl, isobutyl, 2-methoxyethyl, cyclopentyl, 3 - methoxypropyl, 3-ethoxypropyl, n-propyl, isopropyl, 2-hydroxyethyl, cyclopropyl, sec-butyl, tert-butyl, or n-hexyl.
12. 根据权利要求 1~11 中任意一项所述的化合物， 其特征在于， 所述！^是羟基， R4是 Ho  The compound according to any one of claims 1 to 11, wherein the ^ is hydroxyl, R4 is Ho
13. 根据权利要求 1~11中任意一项所述的化合物， 其特征在于， 所述化合物选自： The compound according to any one of claims 1 to 11, wherein the compound is selected from the group consisting of:
1) (21 ,38,41，51，811,101 ,1111，128,133,141 )-13-[(正丙氨基）甲基]-11-[[3，4，6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； 1) (21, 38, 41, 51, 811, 101, 1111, 128, 133, 141)-13-[(n-propylamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethylamino) -β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1 - oxo-hetero-6-azacyclopentadecane-15-one;
2) (2R，3S，4R,5R,8R,10R,11R,12S,13S，14R)-13- [(环丙基氨基）甲基] -11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10，13-四羟基 -3，5，8，10，12，14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  2) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13- [(cyclopropylamino)methyl]-11-[[3,4,6-trideoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
3) (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-[(正丁基氨基）甲基 ]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10,12，14-六 甲基 -1 -氧-杂 -6-氮杂环十五垸 -15-酮；  3) (2R, 3S, 4R, 5R, 8R, 10R, 1 lR, 12S, 13S, 14R)-13-[(n-butylamino)methyl]-11-[[3,4,6-trideoxy -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1 -oxy-hetero-6-azacyclopentadecane-15-one;
4) (211，38，411,51，81^101 ,111，123，138，141 )-1 [[3,4,6-三脱氧-3-(二甲基氨基)-3-0-己吡喃木 糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-((2-羟基 -3-甲基-苄胺基)甲基) -3，5,8,10,12,14-六甲 基 -1-氧-杂 -6-氮杂环十五浣 -15-酮  4) (211,38,411,51,81^101,111,123,138,141 )-1 [[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-((2-hydroxy-3-methyl-benzylamino)methyl)-3,5 ,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
5) (21^38,41 ,51^811,101 ,11R，12S,13S,14R)-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木 糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5，8，10,12,14-六甲基 -13-((3，4，5-三甲氧基-苄基胺)甲 基) -1-氧-杂 -6-氮杂环十五垸 -15-酮；  5) (21^38,41,51^811,101,11R,12S,13S,14R)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexid Erlycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-((3,4,5 -trimethoxy-benzylamine)methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
6) (21 ,38，41，51，81，101，111，128，138,141 )-13-[(2-甲氧基乙基-氨基）甲基]-1 1-[[3,4，6-三 脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  6) (21, 38, 41, 51, 81, 101, 111, 128, 138, 141)-13-[(2-methoxyethyl-amino)methyl]-1 1-[[3,4,6 -triptylo-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
7) (21 ,35,41，51，81 ,1011,111，128，133，141 )-13-[(哌啶基）甲基]-11-[[3，4,6-三脱氧-3-(二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10，12，14-六甲基 -1- 氧-杂 ·6-氮杂环十五烷 -15-酮；  7) (21,35,41,51,81,1011,111,128,133,141)-13-[(piperidinyl)methyl]-11-[[3,4,6-trideoxy-3 -(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 - hexamethyl-1-oxo-hetero 6-azacyclopentadecane-15-one;
8) (211，38，41，51，81，101，1 11，128，138，1411)-13-[(吗啉基）甲基]-1卜[[3，4,6-三脱氧-3-(二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8,10，12,14-六甲基 -1- 氧-杂 氮杂环十五垸 -15-酮；  8) (211, 38, 41, 51, 81, 101, 1, 11, 128, 138, 1411)-13-[(morpholinyl)methyl]-1 b [[3,4,6-trideoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyl-1-oxo-heterozacyclopentadecane-15-one;
9) (2R,3S，4R,5R,8R，10R,11R，12S，13S,14R)-13- [(叔丁基氨基）甲基] -11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5，8，10，12,14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  9) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13- [(tert-butylamino)methyl] -11-[[3,4,6-trideoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
10) (21 ,38,41，51，81，101 ,111，123,138,1411)-13-[(苄基氨基）甲基]-11-[[3,4,6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12,14-六甲基  10) (21, 38, 41, 51, 81, 101, 111, 123, 138, 1411)-13-[(benzylamino)methyl]-11-[[3,4,6-trideoxy-3-( Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-six Methyl
121  121
替换页 （细则第 26条） -1-氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) -1-oxo-hetero-6-azacyclopentadecane-15-one;
1 1) (211,38，41，51 ,81 ,1(^,1 11 ,128,133，141 )-13-[(环戊氨基）甲基]-11-[[3,4，6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5，8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  1 1) (211, 38, 41, 51, 81, 1 (^, 1 11 , 128, 133, 141 )-13-[(cyclopentylamino)methyl]-11-[[3,4,6-trideoxy -3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
12) (2R,3S，4R,5R,8R，10R，11R，12S,13S,14R)-13- [(苯氨基）甲基] -11-[[3,4，6-三脱氧 -3- (二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10，12，14-六甲基小 氧-杂 -6-氮杂环十五垸 -15-酮；  12) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13- [(phenylamino)methyl]-11-[[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
13) (21，38，41 ,51，81，101，111，128,138，1411)-13-[(1-甲氧基丙氨基)甲基]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8,10，12，14-六 甲基 -1-氧杂 -6-氮杂环十五垸 -15-酮；  13) (21, 38, 41, 51, 81, 101, 111, 128, 138, 1411)-13-[(1-methoxypropylamino)methyl]-11-[[3,4,6-trideoxy -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxa-6-azacyclopentadecane-15-one;
14) (2R，3S，4R，5R，8R，10R，11R，12S，13S，14R)-13- [(正己氨基）甲基] -11-[[3,4,6-三脱氧 -3- (二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5,8,10，12,14-六甲基 -1-氧杂 -6-氮杂环十五垸 -15-酮；  14) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13- [(n-hexylamino)methyl] -11-[[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyl-1-oxa-6-azacyclopentadecane-15-one;
15) (21 ,38,4 ,511，81，101 ,11]，128，138,141 )-13-[(2-乙氧基丙氨基）甲基]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8，10，12，14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  15) (21,38,4,511,81,101,11],128,138,141)-13-[(2-ethoxypropylamino)methyl]-11-[[3,4,6-three Deoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
16) (21，38，4 ,51，81，101 ,111 ,128,138,】41 )-13-[(二乙氨基）甲基]-11-[[3,4,6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  16) (21,38,4,51,81,101,111,128,138,]41)-13-[(diethylamino)methyl]-11-[[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
17) (2 ,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[( N-甲基丁氨基）甲基] -11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10,13-四羟基 -3，5，8，10，12，14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  17) (2,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(N-methylbutylamino)methyl]-11-[[3,4,6- Triphos-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
18) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14 )-13-[( N-甲基丙氨基）甲基] -11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10,13-四羟基 -3，5,8,10，12,14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  18) (2R, 3S, 4R, 5R, 8R, 10R, l lR, 12S, 13S, 14 )-13-[(N-methylpropylamino)methyl] -11-[[3,4,6- Triphos-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
1 ) (21^，38，41，511，81，101 ,111，128，138，141 )-13-[(乙基氨基）甲基]-1 [[3,4，6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12，14-六甲基 小氧.杂 -6-氮杂环十五垸 -15-酮；  1) (21^,38,41,511,81,101,111,128,138,141)-13-[(ethylamino)methyl]-1 [[3,4,6-trideoxy-3 -(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 - hexamethyl small oxygen. hetero-6-azacyclopentadecane-15-one;
20) (2R,3S,4R,5 ,8R,10R,11R,12S,13S,14R)-13-[( -甲基乙氨基）甲基] -11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5,8，10，12,14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  20) (2R, 3S, 4R, 5, 8R, 10R, 11R, 12S, 13S, 14R)-13-[(-methylethylamino)methyl] -11-[[3,4,6-trideoxy -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
21 ) (2R,3S,4R,5R,8R, 10R， 11 R, 12S， 13 S, 14R)- 11 -[[3 ,4,6-三脱氧 -3- (二甲基氨基 )-β-ϋ-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12,14-六甲基 -13-[(2，2，2-三氟乙氨 基)甲基 ]小氧-杂 -6-氮杂环十五烷 -15-酮；  21) (2R,3S,4R,5R,8R, 10R, 11 R, 12S, 13 S, 14R)- 11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β- ϋ-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(2 , 2,2-trifluoroethylamino)methyl]oxy-hetero-6-azacyclopentadecane-15-one;
22) (2¾38,411，511，81，1011，111 ,128，138,141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡喃木 糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12,14-六甲基 -13-[(3-硝基苄基氨基)甲基] -1- 氧-杂 *6-氮杂环十五垸 -15-酮  22) (23⁄438,411,511,81,1011,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(3-nitrobenzylamino) )methyl]-1-oxo-hetero*6-azacyclopentadecane-15-one
122  122
替换页 （细则第 26条) 23) (21 ,38,41，51 ,81，1011，1 11，128，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-[(1-羟基 -乙基氨基) -甲基 ]-3，5,8，10,12，14- 六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) 23) (21,38,41,51,81,1011,1 11,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-卩-0 -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(1-hydroxy-ethylamino)-methyl]-3,5,8 ,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
24) (21，38，411，511，81 ,101，1 11，128,138，1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基] -13- [(二甲基氨基)甲基] -2-乙基 -3,4, 10,13-四羟基 -3，5,8,10，12,14-六甲 基 -1_氧-杂 -6-氮杂环十五烧 -15-酮；  24) (21,38,411,511,81,101,11,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyran Xylose]oxy] -13-[(dimethylamino)methyl]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-six Methyl-1_oxy-hetero-6-azacyclopentadecane-15-one;
25) (211,33，411，51，81 ,101^1 111，128，138,141 -11-[[3，4，6-三脱氧-3-(二甲基氨基）-3-0-己吡 喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -13- [(咪唑基）甲基] -3,5,8,10,12,14-六甲基 -1- 氧-杂 -6-氮杂环十五烷 -15-酮；  25) (211,33,411,51,81,101^1 111,128,138,141 -11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexididine Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(imidazolyl)methyl] -3,5,8,10,12,14-hexa Keith-1-oxo-hetero-6-azacyclopentadecane-15-one;
26) (21 ,38，411，51 ,81，101，1111，128,138，141 )-13-[(双(2-羟乙基）氨基）甲基]-1 1-[[3，4，6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4，10，13-四羟基 -3，5，8，10，12,14- 六甲基— 1_氧-杂 _6_氮杂环十五垸 _15_酮； 26) (21, 38, 411, 51, 81, 101, 1111, 128, 138, 141)-13-[(bis(2-hydroxyethyl)amino)methyl]-1 1-[[3,4,6 -triptylo-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl- 1_oxy-hetero- 6 -nitrozacyclopentadecane- 15 ketone;
27) (2! ,38，41，51，81，101，111 ,123,133,1411)-1 1-[[3,4,6-三脱氧-3-(二甲基氨基）^-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10,12，14-六甲基 -13- [(吡咯)甲基] -1-氧- 杂 -6-氮杂环十五烷 -15-酮；  27) (2!, 38,41,51,81,101,111,123,133,1411)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)^-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(pyrrole)methyl -1-Oxo-hetero-6-azacyclopentadecane-15-one;
28) (21，38,41，51，811，1011,111，128，138，141 )-1 1-[[3，4,6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 -13-{[(1-羟基-乙基） -甲基 -氨] -甲 基}-3,5，8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  28) (21,38,41,51,811,1011,111,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0 -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-{[(1-hydroxy-ethyl)-methyl-amino]-methyl} -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
29) (21，33,41 ,511,811,1011,1111,128，138,141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -13-{ [1，2,3]三氮唑基 -1-甲基 }-1-氧-杂 -6-氮杂环十五垸 -15-酮；  29) (21,33,41,511,811,1011,1111,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{ [1,2,3] Triazolyl-1-methyl}-1-oxo-hetero-6-azacyclopentadecane-15-one;
30) (2R,3S,4R,5R,8R, 1 OR, 11 R， 12S, 13S， 14R)-1 [[3，4，6-三脱氧 -3 - (二甲基氨基 )-p-D-己吡 喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8，10，12,14-六甲基 -13- [(块丙基)氨基甲 基 ]-1-氧-杂 -6-氮杂环十五烷 -15-酮；  30) (2R, 3S, 4R, 5R, 8R, 1 OR, 11 R, 12S, 13S, 14R)-1 [[3,4,6-Trideoxy-3 - (dimethylamino)-pD-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- [(block propyl) Aminomethyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
31) (21 ,38,41，511,811,101 ,1 111,125,138，141 )-1 [[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5,8,10,12,14-六甲基 -13-(2-甲基-咪唑小基 -甲基 )-1-氧-杂 -6-氮杂环十五垸 -15-酮；  31) (21,38,41,511,811,101,1 111,125,138,141 )-1 [[3,4,6-Trideoxy-3-(dimethylamino)-indole-0-hexylopyranosyl]oxygen -2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(2-methyl-imidazolyl-methyl) -1-oxo-hetero-6-azacyclopentadecane-15-one;
32) (2!，38，4!，511,81，101，1 111,123，138，141 )-1 1-[[3，4,6-三脱氧-3-(二甲基氨基)^-0-己吡 喃木糖基]氧基] -2-氧 -13- (二乙烯基氨基甲基） -2-乙基 -3,4，10，13-四轻基 -3，5,8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  32) (2!,38,4!,511,81,101,1 111,123,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)^-0 -Hexylpyranosyl]oxy]-2-oxo-13-(divinylaminomethyl)-2-ethyl-3,4,10,13-tetralight-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
33) (21，38，411,51 ,81 ,101 ,1 11 ,128,138,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基）- -0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -13-[(2-羟基 -1-羟基 -甲基 -乙基氨基) -甲 基] -3，5,8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  33) (21,38,411,51 ,81 ,101 ,1 11 ,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)- -0-hexyranium Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(2-hydroxy-1-hydroxy-methyl-ethylamino)-methyl] -3,5 , 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
34) (21 ,38,411，511,81，101 ,111 ,128,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5，8，10,12,14-六甲基 -13- [(甲氨基）甲基 ]- 氧-杂 -6-氮杂环十五垸 -15-酮；  34) (21,38,411,511,81,101,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranose ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(methylamino)methyl]-oxy- Hetero-6-azacyclopentadecane-15-one;
35) (2R,3S,4R,5R,8R, 1 OR, 1 1 R， 12S, 13 S， 14R)- 11 -[[3 ,4，6-三脱氧 -3- (二甲基氨基 )-β-0-己吡  35) (2R,3S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 11 -[[3,4,6-Trideoxy-3-(dimethylamino)- -0-0-hexid
123  123
替换页 （细则第 26条) 喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -13- (异丙氨基-甲基) -3，5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； Replacement page (Article 26) Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(isopropylamino-methyl)-3,5,8,10,12,14-hexa Base-1-oxo-hetero-6-azacyclopentadecane-15-one;
36) (211，33，41，51，811，1011，1 11，128,138，141^)-1 1-[[3,4,6-三脱氧-3-(二甲基氨基)-3-0-己吡 喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5，8,10，12,14-六甲基 -13-[(3-甲基-丁基氨 基) -甲基 ]-1-氧-杂 -6-氮杂环十五院 -15-酮；  36) (211,33,41,51,811,1011,1 11,128,138,141^)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0 -hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(3- Methyl-butylamino)-methyl]-1-oxo-hetero-6-azetidine fifteenth hospital-15-one;
37) (211，38，41 ,51，811,1011,1 111,128，138，141 )-13-[(^杂环丙垸基）甲基]-11-[[3，4，6-三脱氧 - 二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10,13-四羟基 -3,5,8,10,12，14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  37) (211, 38, 41, 51, 811, 1011, 1 111, 128, 138, 141)-13-[(^-heteropropyl)methyl]-11-[[3,4,6-trideoxy - Dimethylamino)-β-D-hexyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
38) (2R,3S,4R，5R,8R,10R，1 1R，12S,13S,14R)-13- [(二乙基氨基）甲基] -11 -[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10,12，14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  38) (2R, 3S, 4R, 5R, 8R, 10R, 1 1R, 12S, 13S, 14R)-13- [(diethylamino)methyl] -11 -[[3,4,6-trideoxy -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
39) (2R，3S,4R,5R,8R,10R，11R，12S，13S,14R)-13- [(环戊基-氨基）甲基 ]-11 -[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8,10，12,14-六 甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  39) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13- [(cyclopentyl-amino)methyl]-11 -[[3,4,6-trideoxy -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
40) (21，38,41，51 ,811，101 ,1 11，128,138，141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基)-3-0-己吡 喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 -13-[(4-甲氧基 -苄基氨基） -甲 基] -3，5,8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  40) (21,38,41,51,811,101,1 11,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(4-methoxy-benzylamino)-methyl] -3,5,8 , 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
41) (21 ,38,411,511,811，101 ,111 ,125，138,141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8，10，12，14-六甲基 -13-[(4-硝基-苄基氨 基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮；  41) (21,38,411,511,811,101,111,125,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyranidyl] Oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(4-nitro-benzylamino)- Methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
42) (21，38，41，51，811，101，1 11，128，133，141 )-13-[(4-氯-苄基氨基）甲基]-1 1-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8,10,12，14-六 甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  42) (21,38,41,51,811,101,1 11,128,133,141 )-13-[(4-chloro-benzylamino)methyl]-1 1-[[3,4, 6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 , 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
43) (211,33，41，51，81，101 ,1111，128，133,141 )-13-[(3，4-二氟-苄基氨基）甲基]-11-[[3，4，6-三 脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  43) (211, 33, 41, 51, 81, 101, 1111, 128, 133, 141)-13-[(3,4-difluoro-benzylamino)methyl]-11-[[3,4,6 -triptylo-3-(dimethylamino)-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
44) (21，38,41，51 ,81，101 ,111 ,123,138,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)- -0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5，8，10,12，14-六甲基 -13- [(甲基- (吡啶 -4- 基） -氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五烷 -15-酮；  44) (21,38,41,51,81,101,111,123,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)- -0-hexyryl xylose Ethyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- [(methyl-(pyridine-4- -amino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
45) (21，38，41，51，81，101，1 11，128，138，141 )-13-[(2，6-二氟-苄氨基）甲基]-11-[[3,4,6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10，12,14- 六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  45) (21,38,41,51,81,101,1 11,128,138,141 )-13-[(2,6-difluoro-benzylamino)methyl]-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
46) (211,38,41^，51，81 ,101 ,1 1^128,138，141 )-13-[(4-氟-苄基氨基）甲基]-11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12,14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  46) (211, 38, 41^, 51, 81, 101, 1 1^128, 138, 141)-13-[(4-fluoro-benzylamino)methyl]-11-[[3,4,6- Triphos-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
47) (21 ,38，41，51 ,81，101，1 11 ,128，138，1411)-13-[(3-氟-苄基氨基）甲基]-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5，8,10，12,14-六  47) (21,38,41,51,81,101,1 11 ,128,138,1411)-13-[(3-fluoro-benzylamino)methyl]-11-[[3,4,6 -triptylo-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-six
124 124
替换页 （细则第 26条) 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) Methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
48) (211，38，41，51，81，101，1 111,128,133，141 )-13-[(2-氟-苄基氨基）甲基]-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5,8,10,12，14-六 甲基 -1 -氧-杂 -6-氮杂环十五烷 -15-酮；  48) (211, 38, 41, 51, 81, 101, 1 111, 128, 133, 141)-13-[(2-fluoro-benzylamino)methyl]-11-[[3,4,6-trideoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyl-1-oxo-6 heteroazacyclopentadecane-15-one;
49) (21，38，41，51，81，101 ,1 11 ,123，138，14] )-13-[(2，4-二氟-苄基氨基）甲基]-1 1-[[3，4，6-三 脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5，8,10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  49) (21,38,41,51,81,101,1 11 ,123,138,14] )-13-[(2,4-Difluoro-benzylamino)methyl]-1 1-[[ 3,4,6-Trideoxy-3-(dimethylamino)-pD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 , 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
50) (21，38,41，51，81，1011,1 11，123,138,1411)-13-[(2,5-二氟-苄基氨基）甲基]-1 1-[[3，4,6-三 脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3,5,8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  50) (21,38,41,51,81,1011,1 11,123,138,1411)-13-[(2,5-difluoro-benzylamino)methyl]-1 1-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-indole-hexyranose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
51) (2 ，38，41，51 ,811，101，1111，123,138，1411)-13-[(3,5-二氟-苄基-氨基）甲基]-11-[[3，4,6-三 脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 -3,5,8，10,12,14-六甲基 -1 -氧-杂 -6-氮杂环十五烷 -15-酮；  51) (2,38,41,51,811,101,1111,123,138,1411)-13-[(3,5-Difluoro-benzyl-amino)methyl]-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
52) (2R,3S,4R，5R,8R， 1 OR, 11 R， 12S, 13 S， 14R)- 11 -[[3,4,6-三脱氧 -3- (二甲基氨基）-β-ϋ-己吡 喃木糖基]氧基] -2-乙基 -13-[4-(4-氟-苯基） -哌嗪 -1 -基-甲基] -3，4，10,13-四羟基 -3,5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  52) (2R, 3S, 4R, 5R, 8R, 1 OR, 11 R, 12S, 13 S, 14R)- 11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β -ϋ-hexylpyranosyl]oxy]-2-ethyl-13-[4-(4-fluoro-phenyl)-piperazine-1-yl-methyl]-3,4,10, 13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
53) (21，38,41 ,51，81 ,1011,1 11 ,128,138,1411)-13-[(2-三氟甲基-苄基氨基）甲基]-11-[[3,4，6- 三脱氧 -3-(二甲基氨基 H3-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3,5,8，10,12,14-六甲基 -1 -氧-杂 -6-氮杂环十五垸 -15-酮；  53) (21, 38, 41, 51, 81, 1011, 1 11 , 128, 138, 1411)-13-[(2-trifluoromethyl-benzylamino)methyl]-11-[[3,4, 6-Trideoxy-3-(dimethylaminoH3-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyl-1 -oxo-hetero-6-azacyclopentadecane-15-one;
54) (211，38，41，51，811，101，1 11，128，138，1411)-13-[(4-三氟甲基-苄基氨基）甲基]-11-[[3,4,6- 三脱氧 -3-(二甲基氨基 H3-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3,5，8,10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  54) (211, 38, 41, 51, 811, 101, 1, 11, 128, 138, 1411)-13-[(4-trifluoromethyl-benzylamino)methyl]-11-[[3, 4,6-Trideoxy-3-(dimethylaminoH3-D-hexylpyranosyl)oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 , 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
55) (2R,3S,4R,5R,8R,10R,l lR，12S，13S,14R)-13-[(3-三氟甲基 -苄基氨基）甲基] -1卜[[3,4,6- 三脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3,5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  55) (2R, 3S, 4R, 5R, 8R, 10R, l lR, 12S, 13S, 14R)-13-[(3-trifluoromethyl-benzylamino)methyl]-1b [[3, 4,6-Trideoxy-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 , 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
56) (2R,3S,4R,5R,8R,10R,11 ,12S,13S,14R) -13-{[ 乙 基 -(2-氟 -苯基） -氨基 ] - 甲 基}-1 1-[[3,4，6-三脱氧-3-(二甲基氨基)^-0-己吡喃木糖基]氧基]-2-乙基-3,4，10,13-四 羟基 -3,5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  56) (2R,3S,4R,5R,8R,10R,11,12S,13S,14R) -13-{[ethyl-(2-fluoro-phenyl)-amino]-methyl}-1 1- [[3,4,6-Trideoxy-3-(dimethylamino)^-0-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy- 3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
57) (2R,3 S,4R, 5R, 8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 13 - { [ 乙 基 -(3- 氟 - 苯 基 ） -氨 基 ] - 甲 基}-11 -[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四 羟基 -3，5,8,10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  57) (2R,3 S,4R, 5R, 8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 13 - { [ethyl-(3-fluoro-phenyl)-amino] - methyl }-11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10, 13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-6-azacyclopentadecane-15-one;
58) (2R,3S，4R，5R,8R，10R，l lR，12S,13S，14R)-13-[(2-氟 -6-三氟甲基-苄基-氨基）甲基] -11-[[3，4，6- 三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4，10，13-四羟基 -3，5,8，10，12，14- 六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮  58) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-fluoro-6-trifluoromethyl-benzyl-amino)methyl]-11 -[[3,4,6-tripodeoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra Hydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
59) (21 ,38,411,511，811,101，1 11，125,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基） -0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13- [(甲基- (吡啶 -3- 基) -氨基) -甲基 ]-1 -氧-杂 -6-氮杂环十五烷 -15-酮；  59) (21,38,411,511,811,101,11,125,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexylopyranosyl]oxy ]-2-Ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(methyl-(pyridin-3-yl)-amino -methyl]-1 -oxo-hetero-6-azacyclopentadecane-15-one;
125  125
替换页 （细则第 26条) 60) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4-羟基 -3-甲 _基— -苄基氨基） -甲 基] -11-[[3,4，6-三脱氧 -3-(二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟 基 -3,5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮； Replacement page (Article 26) 60) (2R, 3S, 4R , 5R, 8R, 10R, l lR, 12S, 13S, 14R) -13 - [(4- hydroxy-3-yl _ - - benzylamino) - methyl] -11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra Hydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-6-azacyclopentadecane-15-one;
61) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 13 - {苯并 [1,3]二氧 -5-基 -氨基甲基） } -11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10,12,14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  61) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 13 - {Benzo[1,3]dioxo-5-yl-aminomethyl) } -11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13 -tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
62) (2R,3 S，4R，5R，8R， 10R， 11 R， 12S， 13S， 14R)- 11 -[[3,4,6-三脱氧 -3- (二甲基氨基）-p-D-己吡 喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-[(3-甲氧基-苄基氨 基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮；  62) (2R,3 S,4R,5R,8R, 10R, 11 R, 12S, 13S, 14R)- 11 -[[3,4,6-Trideoxy-3-(dimethylamino)-pD- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(3-A Oxy-benzylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
63) (2 ,38,4!，51，81，1011，1111，128,138,141 )-13-[(2-甲氧基-苄基氨基)-甲基]-11-[[3，4,6-三 脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  63) (2,38,4!,51,81,1011,1111,128,138,141)-13-[(2-methoxy-benzylamino)-methyl]-11-[[3,4,6- Trideoxy-3-(dimethylamino)-PD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
64) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-( (吡啶 -2-基） -氨基 -甲基 )-11-[[3，4,6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10,12，14- 六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  64) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-((pyridin-2-yl)-amino-methyl)-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 ,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
65) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[ (2-甲氧基 -乙基氨基）甲基] -11-[[3，4，6-三 脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  65) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-methoxy-ethylamino)methyl]-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-indole-hexyranose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
66) (2R,3S,4R,5R,8R, 1 OR, 11R, 12S, 13S, 14R)- 13-{[(2- 羟 基 -N- 甲 基 - 乙 氨 基 ] - 甲 基 }-1 1-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四 羟基 -3,5，8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  66) (2R,3S,4R,5R,8R, 1 OR, 11R, 12S, 13S, 14R)- 13-{[(2-hydroxy-N-methyl-ethylamino)-methyl}-1 1- [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
67) (21，38，41，51，81 ,1011,1111,123，133,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12,14-六甲基 -13-{ [(吡啶 -2-基-甲 基) -氨基] -甲基 }-1-氧-杂 -6-氮杂环十五垸 -15-酮；  67) (21,38,41,51,81,1011,1111,123,133,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{[(pyridine- 2-yl-methyl)-amino]-methyl}-1-oxo-hetero-6-azacyclopentadecane-15-one;
68) (21 ,38,41，511,811，101 ,111 ,128，133,141 )-13-[ (羟基氨基）甲基]-11-[[3,4，6-三脱氧-3-(二 甲基氮基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10，12，14-六甲基 小氧 -杂-6-氮杂环十五垸 -15-酮；  68) (21,38,41,511,811,101,111,128,133,141)-13-[(hydroxyamino)methyl]-11-[[3,4,6-trideoxy-3-(dimethyl) Nitrogen) -β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl Small oxygen-hetero-6-azacyclopentadecane-15-one;
69) (2R,3S,4R,5R,8R,10R,l lR,12S，13S,14R)-13-{[(2-羟基-乙基) -氨基] -甲基 }-11-[[3，4,6-三 脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4,10,13-四羟基 -3,5，8,10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  69) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[(2-hydroxy-ethyl)-amino]-methyl}-11-[[3 ,4,6-Trideoxy-3-(dimethylamino)-PD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
70) (21，38，411，51，81 ,1(^，111 ,123，138，1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基)- -0-己吡 喃木糖基]氧基] -2-乙基 -13-{[(3-氟-苯基） -甲基-氨基] -甲基 }-3,4，10，13-四羟基 -3，5,8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  70) (21,38,411,51,81,1(^,111,123,138,1411)-11-[[3,4,6-tripleoxy-3-(dimethylamino)- -0 -hexylopyranosyl]oxy]-2-ethyl-13-{[(3-fluoro-phenyl)-methyl-amino]-methyl}-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
71) (2^35,411，51，81，101，111，123，138，141^)-13-[(6-氯-吡啶-3-基-氨基)-甲基]-1 [[3，4，6- 三脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮：  71) (2^35,411,51,81,101,111,123,138,141^)-13-[(6-chloro-pyridin-3-yl-amino)-methyl]-1 [[3,4 ,6-Trideoxy-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one:
72) (2R,3S，4R，5R，8R，10R，l lR，12S,13S,14R)-U-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡  72) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-U-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D -hexid
126  126
替换页 （细则第 26条） 喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -13-[(4-羟基-正丁基氨基） -甲 基] -3，5,8,10,12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(4-hydroxy-n-butylamino)-methyl] -3,5,8,10 , 12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
73) 4-{(21，38，41，51，811,101 ,111，128,133，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基) -0-己吡喃 木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5，8,10，12,14-六甲基 -15-酮小氧-杂 -6-氮杂环十五 院 -13-基 -甲基 I- 氨基 }-甲基-苯甲酸  73) 4-{(21,38,41,51,811,101,111,128,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexanpyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one small oxygen-hetero-6- Nitrogen heterocyclic fifteenth hospital-13-yl-methyl I-amino}-methyl-benzoic acid
74) (2R,3S,4 ,5R,8R,10R,11R,12S,13S,14 )-13- (2-烯丙基-氨基） -甲基 -11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10，12，14-六 甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  74) (2R,3S,4,5R,8R,10R,11R,12S,13S,14)-13-(2-allyl-amino)-methyl-11-[[3,4,6-three Deoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
75) (2R,3S,4R,5R,8R,10R,1 lR，12S,13S,14R)-13-{[(3-氨基 -1，4，4-三甲基 -环己基-甲基) -氨 基] -甲基 }-11 -[[3,4,6-三脱氧 -3-(二甲基氨基 )-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3,5，8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  75) (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-{[(3-amino-1,4,4-trimethyl-cyclohexyl-methyl) -amino]-methyl}-11-[[3,4,6-trideoxy-3-(dimethylamino)-PD-hexylopyranosyl]oxy]-2-ethyl-3, 4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
76) (2! ,38，41 ,51，81 ,1011，111 ,128，135,1411)-11-[[3,4，6-三脱氧-3-(二甲基氨基）^-0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -13-{[2-(2-羟基-乙基-氨基) -乙基氨基] -甲 基}-3，5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  76) (2!, 38,41,51,81,1011,111,128,135,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)^-0- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-{[2-(2-hydroxy-ethyl-amino)-ethylamino]- }}-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
77) (21，38，41，51，81，101^1111，123，138,141 )-13-[(2-氯-4-甲氧-苄基氨基)-甲基]-11-[[3，4，6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5,8，10,12，14-六甲 基 -1-氧-杂 -6-氮杂环十五烷 -15-酮  77) (21, 38, 41, 51, 81, 101^1111, 123, 138, 141)-13-[(2-chloro-4-methoxy-benzylamino)-methyl]-11-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 ,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
78) (21，38，411，51 ,811，101 ,111 ,125,138，141 )-1 1-[[3，4,6-三脱氧-3-(二甲基氨基）-3-0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5，8,10，12,14-六甲基 -13-[(1-甲基 -3-苯基- 丙基.氨基) -甲基 ]小氧-杂 -6-氮杂环十五烷 -15-酮；  78) (21,38,411,51,811,101,111,125,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(1-methyl) -3-phenyl-propyl.amino)-methyl]oxy-hetero-6-azacyclopentadecane-15-one;
79) (21，38，411,51 ,811，1011,1111,123,135，1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基）-&-0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5，8，10，12，14-六甲基 -13-哌嗪 -1-基-甲基小 氧-杂 -6-氮杂环十五烷 -15-酮；  79) (21,38,411,51,811,1011,1111,123,135,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-&-0-hexid Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-piperazin-1-yl- Methyl small oxygen-hetero-6-azacyclopentadecane-15-one;
80) (21 ,38，41，511，81，101 ,1111，128,138，141 -1 [[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8，10,12,14-六甲基 -13-{[ (吡啶 -4-基-甲 基) -氨基] -甲基 }-1-氧-杂 -6-氮杂环十五垸 -15-酮；  80) (21,38,41,511,81,101,1111,128,138,141 -1 [[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyranium) Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{[(pyridin-4-yl- Methyl)-amino]-methyl}-1-oxo-hetero-6-azacyclopentadecane-15-one;
81) (21 ,38，4 ,511581^101 511 128,138,1411)-13-{[(3-氯-卩比啶-4-基）甲基氨基]甲基}-11-[[3，4,6- 三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8，10，12，14- 六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮 81) (21,38,4,511 5 81^101 5 11 128,138,1411)-13-{[(3-chloro-indolyl-4-yl)methylamino]methyl}-11-[[ 3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 ,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
82) ^{(21 ,38，411，51，811,1011，111，128，138，141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0- 己吡喃木糖基〗氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -15-酮 -1-氧-杂 -6- 氮杂环十五垸 -13-基-甲基}-2，2，2-三氟-乙酰胺；  82) ^{(21 , 38,411,51,811,1011,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-indole- 0-Hexylpyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one-1 - oxo-hetero-6-azabicyclopentadepin-13-yl-methyl}-2,2,2-trifluoro-acetamide;
83) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[(2-氯-吡啶 -4-基-甲基） -氨基] -甲 基}-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四 羟基 ^,δ,δ,ΙΟ, , -六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮：  83) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-{[(2-chloro-pyridin-4-yl-methyl)-amino]-methyl} -11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13 -tetrahydroxy, δ, δ, ΙΟ, , - hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one:
84) (2R，3S,4R，5R，8R，10R，l lR，12S，13S,14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木  84) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-hexylpyran
127  127
替换页 （细则第 26条） 糖基]氧基] -2_乙基 -3，4，10，13-四羟基 -I3- [(正戊基-氨基) -甲基 ]-3，5，8，10,12，14-六甲基小氧- 杂 -6·氮杂环十五垸 -15-酮 Replacement page (Article 26) Glycosyl]oxy] - 2 -ethyl-3, 4 , 10,1 3 -tetrahydroxy-I 3 - [(n-pentyl-amino)-methyl]-3,5,8,10,12, 14-hexamethyloxy-hetero-6·azacyclopentadecane-15-one
85) (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(1H-苯 并 咪 唑 -2-基 -氨 基） - 甲 基] -11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟 基 -3,5,8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  85) (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(1H-benzimidazol-2-yl-amino)-methyl]-11-[[3 ,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
86) (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R) -13-(Ν，Ν'-二甲基 -肼基 -甲基 )-11-[[3，4，6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10，12，14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  86) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R) -13-(Ν,Ν'-dimethyl-indolyl-methyl)-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
87) (2R,3S,4R,5R，8R，10R,l lR，12S，13S，14R)-13-[(2,6-二氟 -4-甲氧-苄基-氨基）甲基] -11-[[3，4,6- 三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8,10,12,14- 六甲基小氧-杂 -6-氮杂环十五焼 -15-酮  87) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2,6-difluoro-4-methoxy-benzyl-amino)methyl] - 11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13- Tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one
88) (2R,3 S，4R，5R，8R， 1 OR, 11 R, 12S， 13 S, 14R)- 11 -[[3,4,6-三脱氧 -3- (二甲基氨基 )-β-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-{[2-(2-羟基-乙氧基) -乙基氨基] -甲 基}-3，5，8，10,12，14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  88) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 11 -[[3,4,6-Trideoxy-3-(dimethylamino)- β-0-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-{[2-(2-hydroxy-ethoxy)-ethylamino ] -methyl}-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
89) (21 ,38，41，51，81，101，111，128，138，141 )-13-[(2-氯-乙基氨基)-甲基]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -卩 -D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10，12，14-六 甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  89) (21,38,41,51,81,101,111,128,138,141 )-13-[(2-chloro-ethylamino)-methyl]-11-[[3,4,6 -triptylo-3-(dimethylamino)-indole-D-hexyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
90) 2-{(211,38，41，51，81 ,101 ,1 11 ,128，138，141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基)-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10，12，14-六甲基 -15-酮小氧-杂 -6-氮 杂环十五垸 -13-基-甲基] -氨基 }-丁酸；  90) 2-{(211,38,41,51,81,101,1 11 ,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-卩-0-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one Small oxygen-hetero-6-azacyclopentadecanofluoren-13-yl-methyl]-amino}-butyric acid;
91) 3-{(211，38,41，51 ,811，101，111，123，138,1411)-11-[[3，4,6-三脱氧-3-(二甲基氨基)- -0-己 吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -15-酮 -1-氧-杂 -6-氮 杂环十五垸 -13-基-甲基] -氨基 丙酸；  91) 3-{(211,38,41,51,811,101,111,123,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)- - 0-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one-1 - oxo-hetero-6-azetidine, heptadec-13-yl-methyl]-aminopropionic acid;
92) (211,38,41 ,51，81，101 ,1111，128，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基 ]-2-乙基 -13-[(4-氟 -2-硝基 -苯基氨基） -甲基 ]-3,4,10,13-四羟基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  92) (211, 38, 41, 51, 81, 101, 1111, 128, 138, 141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0- Hexylpyranosyl]oxy]-2-ethyl-13-[(4-fluoro-2-nitro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy-3 , 5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
93) (211,38,41 ,511，81 ,1011,1111,128,133,141 )-13-[(4-溴-2-氟-苯基氨基)-甲基]-11-[[3，4，6-三 脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 -3，5，8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  93) (211, 38, 41, 511, 81, 1011, 1111, 128, 133, 141)-13-[(4-bromo-2-fluoro-phenylamino)-methyl]-11-[[3,4,6 -triptylo-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
94) (211,38，41 ,51，81，101，1111，128，138,141 )-13-[(4-溴-2-氨基-嘧啶)-甲基]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮  94) (211, 38, 41, 51, 81, 101, 1111, 128, 138, 141)-13-[(4-bromo-2-amino-pyrimidine)-methyl]-11-[[3,4,6 -triptylo-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
95) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,5-双-三氟甲基 -苯基氨基） -甲 基] -U-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟 基 -3，5,8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  95) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,5-bis-trifluoromethyl-phenylamino)-methyl] -U -[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra Hydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
96) (2 ，38，4! ,511，81，101，1 111，128,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基 ]-2-乙基 -13-[(2,4-二硝基 -苯基氨基） -甲基 ]-3,4,10,13-四羟基  96) (2,38,4!,511,81,101,1 111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexididine Iso-xylyl]oxy]-2-ethyl-13-[(2,4-dinitro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy
128  128
替换页 （细则第 26条） -3,5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
97) (21，33，4!，51 ,81 ,1011，111 ,123,138,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)^-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -13-{ [(吗啉 -4-基-甲 基) -氨基] -甲基 }1-氧-杂 -6-氮杂环十五垸 -15-酮；  97) (21,33,4!,51,81,1011,111,123,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)^-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{[(morpholin-4-yl) -methyl)-amino]-methyl}1-oxo-hetero-6-azacyclopentadecane-15-one;
98) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 13 -[(4- 氨 基 - 吡 啶 -3- 基 -氨 基 ） - 甲 基] -11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟 基 -3，5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  98) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 13 -[(4-amino-pyridin-3-yl-amino)-methyl]-11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra Hydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
99) (21，38,41 ,51 ,81，101 ,111 ,128,138,141 )-13-[(2-氯-苄基氨基)-甲基]-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10，12，14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  99) (21,38,41,51,81,101,111,128,138,141)-13-[(2-chloro-benzylamino)-methyl]-11-[[3,4,6-trideoxy- 3-(Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
100) (21，38，411，51，81，101，111，123，138，1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基)-3-0-己吡 喃木糖基]氧基 ]-2-乙基 -13-[(2，4-二甲基 -苯基氨基） -甲基 ]-3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  100) (21,38,411,51,81,101,111,123,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0- Hexylpyranosyl]oxy]-2-ethyl-13-[(2,4-dimethyl-phenylamino)-methyl]-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
101) (2 ，38，41，511，81^101，111 ,128,138，141 -13-[(3-氯-苯基氨基)-甲基]-11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8,10，12,14-六 甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  101) (2,38,41,511,81^101,111,128,138,141 -13-[(3-chloro-phenylamino)-methyl]-11-[[3,4,6-tripleoxy -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
102) (2R,3S,4R，5R,8R,10R,llR,12S，BS，14R)-13-{[(5-氨基 -1,3,3-三甲基 -环己基甲基 1)-氨 基] -甲基 }-11-[[3,4,6-三脱氧 -3-(二甲基氨基 Π-Ό-己吡喃木糖基]氧基 ]-2-乙基 -3，4,10,13-四羟基 -3，5，8，10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  102) (2R,3S,4R,5R,8R,10R,llR,12S,BS,14R)-13-{[(5-amino-1,3,3-trimethyl-cyclohexylmethyl 1)- Amino]-methyl}-11-[[3,4,6-trideoxy-3-(dimethylaminoindole-indole-hexyranoxy)oxy]-2-ethyl-3,4 ,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
103) (21 ,38，41 ?51 ,81，1011，111，128，135，1411)-13-((2,3-二氯-6-硝基-苄基氨基）甲基)-11-[[3，4，6- 三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10，12，14- 六甲基 _1-氧-杂 _6-氮杂环十五焼 _15_酮 103) (21,38,41 ? 51 ,81,1011,111,128,135,1411)-13-((2,3-dichloro-6-nitro-benzylamino)methyl)-11- [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8,10,12,14- hexamethyl _1- oxo - heteroaryl _ 6 - azetidin fifteen firing _1 _ 5-one
104) (211,38，411,51，811,1011,111，128，138，141 )-13-[(4-氯-苯基氨基)-甲基]-11-[[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5,8,10,12,14-六 甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  104) (211, 38, 411, 51, 811, 1011, 111, 128, 138, 141)-13-[(4-chloro-phenylamino)-methyl]-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 , 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
105) (2R，3S，4R，5R，8R, 10R， 11 R, 12S， 13 S, 14R)- 1 [[3 ,4，6-三脱氧 -3 - (二甲基氨基 )-β-ϋ-己吡 喃木糖基]氧基] -2-乙基 -3，4,10,13-四羟基 -3,5，8，10，12，14-六甲基 -13- (喹啉 - 6-基-氨基甲 基) -1·氧-杂 -6-氮杂环十五垸 -15-酮；  105) (2R,3S,4R,5R,8R, 10R, 11 R, 12S, 13 S, 14R)- 1 [[3,4,6-Trideoxy-3 - (dimethylamino)-β-ϋ -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- (quinoline- 6-yl-aminomethyl)-1 oxo-hetero-6-azacyclopentadecane-15-one;
106) (21，38，41，51，81，101 ,1111，128,138，1411)-11-[[3,4，6-三脱氧-3-(二甲基氨基）^-0-己吡 喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -13-[(3-羟基 -丙基氨基) -甲基 ]-3,5,8,10,12,14- 六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  106) (21,38,41,51,81,101,1111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)^-0-hexanpyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-hydroxy-propylamino)-methyl]-3,5,8,10,12 , 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
107) (2 ,38，41，51 ,81，101 ,111 ,128,133,141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12，14-六甲基 -13- (吗啉 -4-基-氨基甲 基) -1-氧-杂 -6-氮杂环十五垸 -15-酮；  107) (2,38,41,51,81,101,111,128,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranose ]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(morpholin-4-yl-aminomethyl -1-oxo-hetero-6-azacyclopentadecane-15-one;
108) (21，38，41，51 ,81，101，111，128，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）^-0-己吡 喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5，8，10,12,14-六甲基 -13-[(2-甲基氨基 -乙基 氨基).甲基]小氧-杂 -6-氮杂环十五垸 -15-酮；  108) (21,38,41,51,81,101,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)^-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(2-methyl) Amino-ethylamino).methyl]oxy-hetero-6-azacyclopentadecane-15-one;
129  129
替换页 （细则第 26条） 109) (21，33，41，51，81，101 ,111 ,123,133,141 )-13-环庚基氨基甲基-11-[[3,4,6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5，8，10，12，14-六甲基 小氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) 109) (21,33,41,51,81,101,111,123,133,141 )-13-cycloheptylaminomethyl-11-[[3,4,6-trideoxy-3-(dimethylamino) -β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy- Hetero-6-azacyclopentadecane-15-one;
1 10) 4-{(21，38，41，511，811,101 ,111 ,128，138,141 )-11-[[3，4,6,-三脱氧-3-(二甲基氨基) -0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10，12,14-六甲基小氧 -15-酮-杂 -6-氮 杂环十五垸 -13-基-甲基]-氨基 酞腈；  1 10) 4-{(21,38,41,511,811,101,111,128,138,141 )-11-[[3,4,6,-Trideoxy-3-(dimethylamino)-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-1-one-hetero- 6-azacyclopentadepin-13-yl-methyl]-aminophthalonitrile;
1 1 1) (2 ,38,411，51，811,1011，1 11，123，133，1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基）^-0-己吡 喃木糖基]氧基] -2-乙基 -13-{ [(呋喃 -2-基-甲基） -氨基] -甲基 }-3，4，10,13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  1 1 1) (2,38,411,51,811,1011,1 11,123,133,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)^-0- Hexylpyranosyl]oxy]-2-ethyl-13-{[(furan-2-yl-methyl)-amino]-methyl}-3,4,10,13-tetrahydroxy-3 , 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
1 12) (2R,3S，4R,5R,8R，10R，l lR，12S，13S，14R)-l l-[[3，4,6-三脱氧 -3- (二甲基氨基） -β-D-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-[(3-甲氧基-苯氨基) -甲基 ]-3，5，8，10,12，14- 六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  1 12) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β -D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-methoxy-phenylamino)-methyl]-3, 5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
1 13) (21 ,38，41 ,51，81，101^111，128,138,1411)-13-[(3-溴-苯基氨基)-甲基]-11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8,10，12,14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  1 13) (21,38,41,51,81,101^111,128,138,1411)-13-[(3-bromo-phenylamino)-methyl]-11-[[3,4,6- Triphos-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
114) (21，38，411，51，81 ,101，1111，123,138,14 )-1 1-[[3,4，6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5，8,10，12,14-六甲基 -13-[(N-甲基-苯基-氨 基) -甲基 ]-1-氧-杂 -6-氮杂环十五烷 -15-酮；  114) (21,38,411,51,81,101,1111,123,138,14 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(N-methyl) -phenyl-amino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
115) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-氨基 -1-甲基 -乙基氨基） -甲基] - 1 1-[[3，4,6-三脱氧-3-(二甲基氨基) -0-己吡喃木糖基]氧基]-2-乙基-3，4，10,13-四羟基 -3，5,8,10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  115) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(2-amino-1-methyl-ethylamino)-methyl] - 1 1- [[3,4,6-Trideoxy-3-(dimethylamino)-0-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 , 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
1 16) (21 ,33,41 ,51，811,101 ,111 ,123，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-3"0-己吡 喃木糖基]氧基] -2-乙基 -13-[(4-乙炔基 -2H-吡唑 -3-基-氨基) -甲基 ]-3，4,10，13-四羟基 -3，5,8，10，12,14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  1 16) (21,33,41,51,811,101,111,123,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3"0-hexyl Pyranopyranyl]oxy]-2-ethyl-13-[(4-ethynyl-2H-pyrazol-3-yl-amino)-methyl]-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
117) (21，38，41，511，81 ,101，111，128,133,141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基） -0-己吡 喃木糖基]氧基] -2-乙基 -13-[(4-乙基 -6-甲基 -[1，3，5]三氮唑 -2-基-氨基) -甲基 ]-3，4，10，13- 四羟基 -3,5,8,10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  117) (21,38,41,511,81,101,111,128,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranose ]oxy]-2-ethyl-13-[(4-ethyl-6-methyl-[1,3,5]triazol-2-yl-amino)-methyl]-3,4, 10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-6-azacyclopentadecane-15-one;
1 18) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4,6-二羟基 -嘧啶 -2-基-氨基） -甲 基] -11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟 基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  1 18) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4,6-dihydroxy-pyrimidin-2-yl-amino)-methyl] - 11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13- Tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
1 19) (211，38，411，51 ,811，101，1 11 ,128，138，141 )-13-癸垸基氨基甲基-11-[[3，4，6-三脱氧-3-(二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12，14-六甲基 -1-氧*杂-6-氮杂环十五烷 -15-酮；  1 19) (211,38,411,51,811,101,1 11 ,128,138,141 )-13-decylaminomethyl-11-[[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyl-1-oxo-6 hetero-6-azacyclopentadecane-15-one;
120) 3-{(2 ，38，41 ,511，81 ,101，1111，128,138，1411)-1 [[3，4，6-三脱氧-3-(二甲基氨基)-&-0-己 吡喃木糖基]氧基 ]-2-乙基 -3，4，10,13-四羟基 -3，5，8,10，12,14-六甲基 -15-酮小氧-杂 -6-氮 杂环十五烷 -13-基-甲基] -氨基 } -正丁酸；  120) 3-{(2 ,38,41 ,511,81 ,101,1111,128,138,1411)-1 [[3,4,6-Trideoxy-3-(dimethylamino)-&-0- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one small oxygen-hetero -6-azacyclopentadecane-13-yl-methyl]-amino}-n-butyric acid;
121) (211，38，41 ,511,81 ,1011,1111，123,138,1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基） -0-己吡  121) (211,38,41,511,81,1011,1111,123,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexididine
130  130
替换页 （细则第 26条） 喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -13-[(1-羟基甲基 -丙基氨基） -甲 基] -3,5,8,10,12,14-六甲基 -1 -氧-杂 -6-氮杂环十五烷 -15-酮； Replacement page (Article 26) Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(1-hydroxymethyl-propylamino)-methyl]-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
122) (2R,3S,4R,5R,8R, 10R,1 1R,12S,13S,14R)- 1 [[3，4，6-三脱氧 -3- (二甲基氨基 )-β-ϋ-己吡 喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5,8,10,12,14-六甲基 -13-[(2-苯基-丙基氨 基) -甲基 ] 1 -氧-杂 -6-氮杂环十五垸 -15-酮；  122) (2R,3S,4R,5R,8R, 10R,1 1R,12S,13S,14R)- 1 [[3,4,6-Trideoxy-3-(dimethylamino)-β-ϋ- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(2-benzene -propylamino)-methyl] 1-oxo-hetero-6-azacyclopentadecane-15-one;
123)磺酸单 -2-{(2R,3S,4R,5R，8R，10R,l lR，12S,13S,14R)- 11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D- 己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12，14-六甲基 -1-氧 -15-酮-杂 -6-氮杂 环十五綜 -13-基-甲基] -氨基 } -乙酯  123) Sulfonic acid mono-2-{(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)- 11-[[3,4,6-trideoxy-3-(dimethyl) Base amino) -β-D-hexyranoxyxy]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl -1-oxo-15-keto-hetero-6-azetidine fifteen-13-yl-methyl]-amino}-ethyl ester
124) (21 ,38,41，51 ,81 ,1011,1 11 ,128,138,1411)-13-[(3，4-二氟-苯基氨基)-甲基]-1 1-[[3，4，6-三 脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5，8,10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  124) (21, 38, 41, 51, 81, 1011, 1 11 , 128, 138, 1411)-13-[(3,4-difluoro-phenylamino)-methyl]-1 1-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-indole-hexyranose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 , 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
125) (21，38，41 ,51 ,811，101，1 11，128，138,1411)-13-[(3,5-二氟-苄基氨基)-甲基]-11-[[3，4，6-三 脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  125) (21,38,41,51,811,101,1 11,128,138,1411)-13-[(3,5-difluoro-benzylamino)-methyl]-11-[[3 ,4,6-Trideoxy-3-(dimethylamino)-PD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
126) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4,4-双 甲 氧基 -正丁基氨基） - 甲 基] -11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟 基 -3，5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  126) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(4,4-Dimethoxy-n-butylamino)-methyl]-11- [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
127) (211,38,41 ,5]1,811，1011,1 11 ,128,138，1411)-13-[(3,4-二氯-苄基氨基)-甲基]-1 1-[[3，4，6-三 脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5，8,10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  127) (211,38,41,5]1,811,1011,1 11 ,128,138,1411)-13-[(3,4-Dichloro-benzylamino)-methyl]-1 1-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-indole-hexyranose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 , 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
128) (21，38，41，51 ,81，101，1111，128，138，141 )-1 [[3，4，6-三脱氧-3-(二甲基氨基） -0-己吡 喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -13-[(2-甲氧基 -乙基氨基） -甲 基] -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  128) (21,38,41,51,81,101,1111,128,138,141 )-1 [[3,4,6-Trideoxy-3-(dimethylamino)-0-hexanpyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(2-methoxy-ethylamino)-methyl]-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
129) (21 ,38,411，51，81，1011,111，128，138，141 )-13-[(4-二乙基氨基-1-甲基-丁基氨基)-甲基]- 1 1-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8:，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  129) (21,38,411,51,81,1011,111,128,138,141)-13-[(4-Diethylamino-1-methyl-butylamino)-methyl]- 1 1- [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8:,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
130) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3-环 己 基氨 基 - 丙 基氨 基） - 甲 基] -11-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟 基 -3,5，8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  130) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3-cyclohexylamino-propylamino)-methyl]-11-[[3, 4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5 , 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
131) (2R，3S,4R，5R，8R,10R,l lR,12S，13S，14R)-13-((3，4-二氯苄基氨基）甲基) -11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5,8,10,12，14-六甲基 小氧-杂 -6-氮杂环十五烷 -15-酮；  131) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-((3,4-Dichlorobenzylamino)methyl)-11-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
132) (21 ,38，411，51，81，101 ,1 11 ,128，138,1411)-1 1-[[3,4,6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5,8，10，12,14-六甲基 -13-[(1-甲基-正丁基氨 基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮；  132) (21,38,411,51,81,101,1 11 ,128,138,1411)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-0- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(1-A -n-butylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
133) (21，38,41 ,51，81 ,1011,111，128，138,141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基）-3-0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -13-[(4-羟基 -3-甲氧基 -苄基氨基) -甲  133) (21,38,41,51,81,1011,111,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(4-hydroxy-3-methoxy-benzylamino)-
131  131
替换页 （细则第 26条) 基] 3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) 3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
134) (21，38,411,51 ,81，1011,1111，128，138,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-[(2-吡啶 -3-基-乙 基氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮；  134) (21,38,411,51,81,1011,1111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranium Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(2-pyridin-3-yl) -ethylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
135) (2^38，41 ,51 ,811，101，111 ,128，138,1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基）^-0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5，8，10，12，14-六甲基 -13-[(3-三氟甲基 -苄基 氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五烷 -15-酮；  135) (2^38,41,51,811,101,111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)^-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(3-trifluoro) Methyl-benzylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
136) (211，38,41，511，81，101 ,1 111,128,138,141 )-13-[(2-氨基-苄基氨基)-甲基]-11-[[3，4,6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5，8,10，12,14- 六甲基小氧.杂 -6_氮杂环十五垸 _15-酮； 136) (211, 38, 41, 511, 81, 101, 1 111, 128, 138, 141)-13-[(2-amino-benzylamino)-methyl]-11-[[3,4,6-trideoxy-3 - (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 - hexamethyloxyxo.hetero- 6 -nitrozacyclopentadecane- 15 -one;
137) (2R,3 S,4R,5R,8R, 1 OR, 11 R， 12S， 13 S， 14R)- 11 - [[3，4,6-三脱氧 -3- (二甲基氨基 )-P-D-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8,10,12，14-六甲基 -13-{[(5-甲基-吡唑 -2- 基-甲基) -氨基] -甲基 氧-杂 -6-氮杂环十五垸 -15-酮；  137) (2R,3 S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)- 11 - [[3,4,6-Trideoxy-3-(dimethylamino)- PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-{[( 5-methyl-pyrazol-2-yl-methyl)-amino]-methyloxy-hetero-6-azacyclopentadecane-15-one;
138) (211，38,41，51 ,811,1011,111，128,138,1411)-11-[[3，4,6-三脱氧-3-(二甲基氨基） -0-己吡 喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -13-[(3-甲氧基 -丙基氨基） -甲 基] -3，5，8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  138) (211,38,41,51,811,1011,111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranium Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-methoxy-propylamino)-methyl]-3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
139) (2R,3S，4R，5R,8R,10R,UR,12S，13S,14R)-13- [(环己基-甲基-氨基） -甲基 ]-11-[[3，4，6-三 脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5，8,10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  139) (2R,3S,4R,5R,8R,10R,UR,12S,13S,14R)-13- [(cyclohexyl-methyl-amino)-methyl]-11-[[3,4,6 -triptylo-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
140) (21，38，41，51，811，101，1111，128,138,141 )-1卜[[3，4,6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8,10,12，14-六甲基 -13-[(1,2,2-三甲基-丙 基氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五垸 -15-酮；  140) (21, 38, 41, 51, 811, 101, 1111, 128, 138, 141) -1 [[3,4,6-Trideoxy-3-(dimethylamino)-indole-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(1,2,2-three Methyl-propylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
141) (211,38,411，51 ,81 ,101，1111，128，138，141 )-1 1-[[3，4,6-三脱氧-3-(二甲基氨基）- -0-己吡 喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3，5，8，10,12，14-六甲基 -13- (哌啶 -4-基-氨基甲 基) -1-氧-杂 -6-氮杂环十五垸 -15-酮；  141) (211,38,411,51,81,101,1111,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)- -0-hexididine Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(piperidin-4-yl -aminomethyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
142) (21 ,38，41，511,8 ，101 ,1111,123,133,141 )-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡 喃木糖基]氧基] -2-乙基 -13-[(2-氟 -苯基氨基) -甲基 ]-3,4,10,13-四羟基 -3，5，8，10，12，14-六 甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  142) (21,38,41,511,8,101,1111,123,133,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-13-[(2-fluoro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
143) (2!，38,411，511，81 ,101，1 11 ,128，138，141 )-1 [[3，4，6-三脱氧-3-(二甲基氨基）^-0-己吡 喃木糖基]氧基] -2-乙基 -13-[(4-氟 -苯基氨基) -甲基 ]-3,4,10,13-四羟基 -3，5，8，10，12，14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  143) (2!,38,411,511,81,101,1 11 ,128,138,141 )-1 [[3,4,6-Trideoxy-3-(dimethylamino)^-0-hexpyridinium Erlycosyl]oxy]-2-ethyl-13-[(4-fluoro-phenylamino)-methyl]-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
144) (2R,3 S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 13 -[(4-二 乙 基 氨 基 -苯 基氨 基 ） - 甲 基] -1_[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟 基 -3,5，8，10,12,14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  144) (2R,3 S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 13 -[(4-diethylamino-phenylamino)-methyl] -1_ [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
145) ^[(21 ,38,411,51 ,811，1011,111，128，138，141 )-11-[[[3,4，6-三脱氧-3-(二甲基氨基)-卩-0-己 吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3,5,8,10,12,14-六甲基 -15-酮 -1-氧-杂 -6-氮 杂环十五垸 -13-基-甲基] -苯甲酰胺；  145) ^[(21 ,38,411,51 ,811,1011,111,128,138,141 )-11-[[[3,4,6-Trideoxy-3-(dimethylamino)-卩-0 -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one-1- Oxy-hetero-6-azacyclopentadepin-13-yl-methyl]-benzamide;
132  132
替换页 （细则第 26条） 146) (21 ,38,41，51，81，1011，111，128,133,1411)-13-[(2,6-二氟-苯基氨基)-甲基]-11-[[3，4，6-三 脱氧 -3-(二甲基氨基 )-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮： Replacement page (Article 26) 146) (21, 38, 41, 51, 81, 1011, 111, 128, 133, 1411)-13-[(2,6-difluoro-phenylamino)-methyl]-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 ,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one:
147) (2R，3S,4R，5R，8R,10R，l lR，12S,13S,14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡 喃木糖基]氧基] -13-[N'-(2,4-二硝基-苯基) -肼基甲基] -2-乙基 -3，4，10,13-四羟基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  147) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-hexylpyranosyl]oxy]-13-[N'-(2,4-dinitro-phenyl)-fluorenylmethyl]-2-ethyl-3,4,10,13 -tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
148) (21 ,38,41，51 ,81 ,101，111，128，138，141 )-13-[(6-氯-卩比啶-2-基-氨基)-甲基]-11-[[3，4,6- 三脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3,5，8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  148) (21,38,41,51,81,101,111,128,138,141 )-13-[(6-chloro-indolyl-2-yl-amino)-methyl]-11-[ [3,4,6-Trideoxy-3-(dimethylamino)-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
149) (211，33,411，51 ,81，101，111，128，138，14 )-13-[(6-溴吡啶-2-基-氨基)-甲基]-11-[[3,4,6-三 脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3,5，8,10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  149) (211,33,411,51,81,101,111,128,138,14 )-13-[(6-bromopyridin-2-yl-amino)-methyl]-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-β-indole-hexyranose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 , 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
150) (21，33,411,51 ,81，101 ,111，128,138，1411)-11-[[3，4,6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基] -2-乙基 -13-肼基甲基 -3，4,10，13-四羟基 -3，5，8，10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  150) (21,33,411,51,81,101,111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranidyl ]oxy]-2-ethyl-13-mercaptomethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-hetero- 6-azacycloheopyridin-15-one;
151) (21，38,41 ,51，8]，101，111，128，138,1411)-13-[(3-氨基-苄基氨基)-甲基]-11-[[3，4,6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12,14- 六甲基小氧-杂 _6-氮杂环十五烷 _15_酮； 151) (21, 38, 41, 51, 8], 101, 111, 128, 138, 1411)-13-[(3-amino-benzylamino)-methyl]-11-[[3,4, 6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 ,10,12,14-hexamethyloxy-hetero- 6 -azacyclopentadecane-15-one;
152) (211，38，41，51^，811,101，111，128,138，141 )-13-[(2-氯-苯基氨基)-甲基]-11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10，12，14-六 甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  152) (211, 38, 41, 51^, 811, 101, 111, 128, 138, 141)-13-[(2-chloro-phenylamino)-methyl]-11-[[3,4,6-trideoxy -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
153) (211，33，41，51^811，101，1111，128，133,1411)-1 [[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12，14-六甲基 -13-(Ν'-苯基-肼基甲 基) -1-氧-杂 -6-氮杂环十五烷 -15-酮；  153) (211,33,41,51^811,101,1111,128,133,1411)-1 [[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(Ν'-phenyl - mercaptomethyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
154) (21 ,38，41 ,5^81 ,1011，1111，128,133,141 )-1 [[3，4，6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基 ]-2-乙基 -3，4，10,13-四羟基 13-{[(1Η-吲哚 -3-基-甲基） -氨基] -甲 基 3，5，8，10,12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  154) (21,38,41,5^81,1011,1111,128,133,141 )-1 [[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranidyl] Oxy]-2-ethyl-3,4,10,13-tetrahydroxy 13-{[(1Η-indol-3-yl-methyl)-amino]-methyl 3,5,8,10, 12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
155) (21，38,4] ,511,81 ,1011，111 ,128，138，141 )-13-[(4-氯-2-硝基-苯基氨基)-甲基]-11-[[3,4，6- 三脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5,8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  155) (21,38,4],511,81,1011,111,128,138,141 )-13-[(4-chloro-2-nitro-phenylamino)-methyl]-11-[ [3,4,6-Trideoxy-3-(dimethylamino)-PD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
156) (2 ,38，4!，51 ,811，101，1 11，128,138,141 )-13-[(3-氯-正丙基氨基)-甲基]-11-[[3,4，6-三脱 氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12，14- 六甲基 -1-氧-杂 _6_氮杂环十五烷 -15-酮； 156) (2,38,4!,51,811,101,1 11,128,138,141 )-13-[(3-chloro-n-propylamino)-methyl]-11-[[3,4,6- Triphos-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyl-1-oxo-hetero- 6 -azacyclopentadecane-15-one;
157) (21 ,38，411，511,81，101，111 ,128,138,1411)-13-[(2-氯-4-硝基-苯基氨基)-甲基]-11-[[3，4,6- 三脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4,10，13-四羟基 -3,5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  157) (21, 38, 411, 511, 81, 101, 111, 128, 138, 1411)-13-[(2-chloro-4-nitro-phenylamino)-methyl]-11-[[3, 4,6-Trideoxy-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8 , 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
158) (21，38，41，51，81，101，111，128,138，141 -1 1-[[3,4，6-三脱氧-3-(二甲基氨基）-3-0-己吡  158) (21,38,41,51,81,101,111,128,138,141 -1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexididine
133  133
替换页 （细则第 26条） 喃木糖基]氧基] -2-乙基 -3,4,10，13-四羟基 -3，5，8，10，12，14-六甲基 -13-[(4-对 -甲基苯氧基 -苯基氨基) -甲基 ]-1-氧-杂 -6-氮杂环十五烷 -15-酮； Replacement page (Article 26) Iso-xylyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-[(4-pair-A) Phenoxy-phenylamino)-methyl]-1-oxo-hetero-6-azacyclopentadecane-15-one;
159) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,5-二 氯 -吡 啶 -4-基 -氨 基） - 甲 基] -11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟 基 -3,5，8,10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  159) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-[(3,5-Dichloro-pyridin-4-yl-amino)-methyl]-11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetra Hydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
160) (2R,3 S ,4R, 5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 13 - [(3 -氨 基 - 吡 啶 -2- 基 -氨 基 ） - 甲 基] -11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟 基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  160) (2R,3 S ,4R, 5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 13 - [(3 -Amino-pyridin-2-yl-amino)-methyl] 11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13- Tetrahydroxy-3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
161) 1-{(21 ,38,41 ,511，81 ,101，111 ,128,138,141 )-[1 1-[[3，4，6-三脱氧-3-(二甲基氨基) -0-己 吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5,8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环 十五垸 -15-酮 -13-基-甲基] -氨基 } -咪唑 -2，4-二酮；  161) 1-{(21 ,38,41 ,511,81 ,101,111 ,128,138,141 )-[1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1-oxo-hetero-6- Nitroheterocyclopentadecane-15-keto-13-yl-methyl]-amino}-imidazole-2,4-dione;
162) (2R,3 S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 13-[(3,5- 二 甲 氧 基 - 苯 基 氨 基 ） - 甲 基] -1 1-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟 基 -3,5，8,10,12，14-六甲基 -15-酮小氧-杂 -6-氮杂环十五垸；  162) (2R,3 S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 13-[(3,5-Dimethoxy-phenylamino)-methyl] -1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10, 13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one small oxygen-hetero-6-azacyclopentadecane;
163) 3-{(211，38，41，511，81，1011，1 111，128,133,1411)-[11-[[3,4，6-三脱氧-3-(二甲基氨基)-3-0-己 吡喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5,8，10，12，14-六甲基 -15-酮 -1-氧-杂 -6-氮 杂环十五垸 -13-基-甲基] -氨基 } -噻吩 -2-羧酸甲酯；  163) 3-{(211,38,41,511,81,1011,1 111,128,133,1411)-[11-[[3,4,6-Trideoxy-3-(dimethylamino)-3) -0-hexylopyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one- Methyl 1-oxo-hetero-6-azabicyclopentadepin-13-yl-methyl]-amino}-thiophene-2-carboxylate;
164) (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-{[3-氯 -1-(2-氯-乙基） -正丙基氨基] -甲 基 }-1 1 -[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10，13-四 羟基 -3,5，8,10，12，14-六甲基 -1 -氧-杂 -6-氮杂环十五垸 -15-酮  164) (2R,3S,4R,5R,8R,10R,1 lR,12S,13S,14R)-13-{[3-chloro-1-(2-chloro-ethyl)-n-propylamino] - Methyl}-1 1 -[[3,4,6-tripodeoxy-3-(dimethylamino)-β-D-hexyranopyranosyl]oxy]-2-ethyl-3,4 ,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-1 -oxo-hetero-6-azacyclopentadecane-15-one
165) (21，38,41 ,51 ,811,1011，111，128，138，141 )-1 1 -[[3，4,6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基 ]-2-乙基 -3,4，10，13-四羟基 -13-[(3-羟基 -吡啶 -2-基-氨基） -甲 基] -3，5,8，10,12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  165) (21,38,41,51,811,1011,111,128,138,141 )-1 1 -[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0 -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-[(3-hydroxy-pyridin-2-yl-amino)-methyl] -3 , 5,8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
166) (21，38,41 ,51，81 ,1011,111 ,128，133,14 -11-[[3,4,6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-异丙基 -硫基 -甲基 -3，5,8，10，12,14-六甲基 -1-氧 *杂 -6-氮杂环十五垸 -15-酮；  166) (21,38,41,51,81,1011,111,128,133,14 -11-[[3,4,6-trideoxy-3-(dimethylamino)-卩-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-isopropyl-thio-methyl-3,5,8,10,12,14- Hexamethyl-1-oxo-6 hetero-6-azacyclopentadecane-15-one;
167) (21，38,41，51 ,81 ,101 ,1 11 ,128，138，1411)-1 1-[[3,4，6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -13-叔丁基 -硫基 -甲基 -3,5，8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  167) (21, 38, 41, 51, 81, 101, 1 11 , 128, 138, 1411)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-indole- 0-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-tert-butyl-thio-methyl-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
168) (2R,3S,4R,5R,8R, 1 OR, 11 R, 12S， 13 S, 14R)-11-[[3 ,4,6-三脱氧 -3- (二甲基氨基 )-β-ϋ-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5,8，10,12，14-六甲基 -13- (萘 -2-基-硫基-甲 基) -1，氧-杂 -6-氮杂环十五烷 -15-酮；  168) (2R,3S,4R,5R,8R, 1 OR, 11 R, 12S, 13 S, 14R)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β -ϋ-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- (naphthalene -2-yl-thio-methyl)-1,oxy-hetero-6-azacyclopentadecane-15-one;
169) (2R,3S,4R,5R,8R,10R,HR,12S,13S,14R)-13-(4,5- 二 氢 - 噻 唑 -2- 基 -硫 基 - 甲 基) -1 1-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10,13-四羟 基 -3，5，8，10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  169) (2R,3S,4R,5R,8R,10R,HR,12S,13S,14R)-13-(4,5-Dihydro-thiazol-2-yl-thio-methyl)-1 [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
170) (2R，3 S,4R,5 ,8R, 1 OR, 1 1 R, 12S， 13 S, 14R)- 13-(2,3-二羟基 -丙基 -硫基 -甲基）- 11 -[[3，4,6- 三脱氧 -3-(二甲基氨基）-P-D-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基- 170) (2R,3 S,4R,5 ,8R, 1 OR, 1 1 R, 12S, 13 S, 14R)- 13-(2,3-dihydroxy-propyl-thio-methyl)- 11 -[[3,4,6-trideoxy-3-(dimethylamino)-PD-hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-
134 134
替换页 （细则第 26条） -3，5，8，10,12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
171) (2R，3S，4R，5R，8R，10R,l lR，12S,13S,14R)-l l-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡 喃木糖基]氧基 ]-2-乙基 -13- (呋喃 -2-基 -甲基 -硫基 -甲基）-3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  171) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-hexylpyranosyl]oxy]-2-ethyl-13-(furan-2-yl-methyl-thio-methyl)-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
172) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-(2-二 乙 基 氨 基 - 乙 基 -硫基 - 甲 基) -11-[[3，4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟 基 -3，5，8,10，12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  172) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-13-(2-diethylamino-ethyl-thio-methyl)-11-[[3 ,4,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3, 5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
173) (211，35，411，51，81，101 ,1 11，128，138，141 )-13-苄基-硫基-甲基-1 [[3，4，6-三脱氧-3-(二甲 基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4，10,13-四羟基 -3，5，8，10，12,14-六甲基小 氧-杂 -6-氮杂环十五烷 -15-酮；  173) (211,35,411,51,81,101,1 11,128,138,141 )-13-benzyl-thio-methyl-1 [[3,4,6-trideoxy-3- (dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14- Hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
174) (2R，3 S,4R,5R，8R，10R，1 1R,12S,13S,14R)- 11 -[[3,4,6-三脱氧 -3- (二甲基氨基）-β-0-己吡 喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -3,5,8,10，12,14-六甲基 -13-Ρ-甲基苯-硫基-甲 基 -1 -氧-杂 -6-氮杂环十五垸 -15-酮；  174) (2R,3 S,4R,5R,8R,10R,1 1R,12S,13S,14R)- 11 -[[3,4,6-Trideoxy-3-(dimethylamino)-β- 0-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-indole-A Alkyl phenyl-thio-methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
175) (211，38,41 ,51 ,81，101 ,1 11，128，138，1411)-13-(4-氯-苯基-硫基-甲基)-1 1-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3,5，8,10,12，14-六 甲基 -卜氧-杂 -6-氮杂环十五烷 -15-酮；  175) (211, 38, 41, 51, 81, 101, 11, 11, 128, 138, 1411)-13-(4-chloro-phenyl-thio-methyl)-1 1-[[3,4 ,6-Trideoxy-3-(dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-o-oxo-hetero-6-azifeicyclopentadecane-15-one;
176) (2!，38,411，51，81，101，1 1] ,128，138,141 )-1 1-[[3,4,6-三脱氧-3-(二甲基氨基）^-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基- -3，5，8,10,12，14-六甲基 -13-正丙基-硫基-甲 基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  176) (2!,38,411,51,81,101,1 1] ,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)^-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3 -5,8,10,12,14-hexamethyl-13-n-propyl-sulfur Base-methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
177) 3-{(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R 11-[[3,4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃 木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3，5，8，10，12，14-六甲基 -15-酮小氧-杂 -6-氮杂环十五 院 -13-基 -甲基 -硫基 丙酸  177) 3-{(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R 11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D -hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one small oxygen- Hetero-6-azetidine fifteenth hospital-13-yl-methyl-thiopropionic acid
178) (21，38,41 ,51，811,101 ,1 111，128,138,141 )-11-[[3,4，6-三脱氧-3-(二甲基氨基） -0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8，10,12，14-六甲基 -13-苯基-硫基-甲基小 氧-杂 -6-氮杂环十五烷 -15-酮；  178) (21,38,41,51,811,101,1 111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexylopyranosyl] Oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-phenyl-thio-methyloxy-hybrid -6-azacyclopentadecane-15-one;
179) (2R，3S，4R，5R,8R,10R，1 1R，12S,13S，14R)-13- (丁基-硫基-甲基) - 11-[[3,4，6-三脱氧 -3- (二 甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  179) (2R,3S,4R,5R,8R,10R,1 1R,12S,13S,14R)-13-(butyl-thio-methyl)-11-[[3,4,6-trideoxy -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
180) (2R，3S，4R,5R,8R， 1 OR, 1 1 R, 12S， 13 S，14R)-1 1-[[3 ,4,6-三脱氧 -3- (二甲基氨基 )-β-ϋ-己吡 喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -13-(3-巯基-丙基-硫基-甲基) -3,5,8,10,12,14- 六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  180) (2R,3S,4R,5R,8R, 1 OR, 1 1 R, 12S, 13 S,14R)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino) -β-ϋ-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(3-indolyl-propyl-thio-methyl)-3 ,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
181) (21 ,38，41，5 ，81，1011，1 111，123，138，1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基)-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12，14-六甲基 -13-戊基 -硫基 -甲基 -1- 氧-杂 -6-氮杂环十五垸 -15-酮；  181) (21,38,41,5,81,1011,1 111,123,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0 -hexylopyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-pentyl-sulfur Base-methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
182) (2R,3S,4R,5R,8R,10R,1 1R,12S,13S,14R)-1 1-[[3,4，6-三脱氧 -3- (二甲基氨基） -β-D-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12,14-六甲基 -13-己基 -硫基 -甲基 -1- 氧-杂 -6-氮杂环十五烷 -15-酮；  182) (2R,3S,4R,5R,8R,10R,1 1R,12S,13S,14R)-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-hexyl-sulfur Base-methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
135  135
替换页 （细则第 26条） 183) (2R，3S，4R，5R,8R,10R,l lR,12S， S,14R)-l l-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-辛基 -硫基 -甲基 -1- 氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) 183) (2R,3S,4R,5R,8R,10R,l lR,12S,S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-octyl- Thio-methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
184) (211,33，41，51，8^101，1 11，128,138，141 )-1 1-[[3，4，6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -13-十二烷基-硫基-甲 基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  184) (211,33,41,51,8^101,1 11,128,138,141 )-1 1-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexididine Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-dodecyl-thio -methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
185) (21，38，411,51，81，101，1 11，123，138，1411)-11-[[3,4，6-三脱氧-3-(二甲基氨基)-3-0-己吡 喃木糖基]氧基] -2-乙基 -13-(3-氟-苄基-硫基-甲基) -3,4,10,13-四羟基 -3，5,8，10,12,14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  185) (21,38,411,51,81,101,1 11,123,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0 -Hexylpyranosyl]oxy]-2-ethyl-13-(3-fluoro-benzyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8 , 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
186) (21 ,38，41 ,51 ,81，101，1 111，128,138，1411)-13-(苯并噻唑-2-基-硫基-甲基)-1 1-[[3，4，6-三 脱氧 -3-(二甲基氨基）-p-D-己吡喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -3，5,8，10,12，14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮；  186) (21, 38, 41, 51, 81, 101, 1 111, 128, 138, 1411)-13-(benzothiazol-2-yl-thio-methyl)-1 1-[[3,4, 6-Trideoxy-3-(dimethylamino)-pD-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10 , 12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
187) {(2R，3S，4R，5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-木 -B比 喃糖基） ]-2-氧 -2-乙基 -3,4,10, 13-四羟基 -3，5，8，10,12，14-六甲基 -15-酮 -1-氧-杂 -6-氮杂 环十五垸 -13-基-甲基-硫基] } -乙酸  187) {(2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β -D-wood-B-pyranosyl)]-2-oxo-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15 -keto-1-oxo--6-azacyclopentadepin-13-yl-methyl-thio] }-acetic acid
188) (211，38,41，51，81，101，111，128,138，141 )-1卜[[3，4，6-三脱氧-3-(二甲基氨基） -0-己吡 喃木糖基]氧基] -2-乙基 -13-(4-氟-苯基-硫基-甲基) -3,4,10,13-四羟基 -3,5,8,10,12,14-六 甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  188) (211, 38, 41, 51, 81, 101, 111, 128, 138, 141) -1 [[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranium Glycosyl]oxy]-2-ethyl-13-(4-fluoro-phenyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
189) (2R,3S,4R,5R,8R, 10R,1 1R,12S,13S,14R)- 1 1 -[[3 ,4,6-三脱氧 -3- (二甲基氨基）-p-D-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-异丁基 -硫基 -甲基 -3，5,8,10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  189) (2R,3S,4R,5R,8R, 10R,1 1R,12S,13S,14R)- 1 1 -[[3,4,6-Trideoxy-3-(dimethylamino)-pD- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-isobutyl-thio-methyl-3,5,8,10,12,14 - hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
190) (2R,3S,4R,5R,8R,10R,11R，12S，13S，14R) - 11-[[3，4，6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木 糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-{ (仲-丁基-硫基） -甲基 3，5,8，10，12，14-六甲基 -1- 氧-杂 _6-氮杂环十五垸 -15-酮  190) (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R) - 11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-{(sec-butyl-thio)-methyl 3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
191) (21 ,38，41，51^811,101，1 111，128,138,141 )-1 1 -[[3,4，6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -13-(2-硫醇-乙基-硫基-甲基) -3,5，8,10,12,14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  191) (21,38,41,51^811,101,1 111,128,138,141 )-1 1 -[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(2-thiol-ethyl-thio-methyl) -3,5,8,10,12 , 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
192) (21，38,41 ,511，811，101 ,1 111,128,133，1411)-11-[[3,4,6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5，8,10，12,14-六甲基 -13-(3-甲基 -丁基 -硫基 -甲基 )-1-氧-杂 -6-氮杂环十五垸 -15-酮；  192) (21, 38, 41, 511, 811, 101, 1 111, 128, 133, 1411) -11-[[3,4,6-trideoxy-3-(dimethylamino)-0-hexyryl xylose ]]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(3-methyl-butyl-sulfur Base-methyl)-1-oxo-hetero-6-azetidine-decaquinone-15-one;
193) (211，38，41 ,51，81 ,101，1 11 ,128,138,141 )-13-(111-苯并咪唑-2-基-硫基-甲基)-11-[[3，4,6- 三脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12，14-六甲基小氧-杂 -6-氮杂环十五烷 -15-酮；  193) (211, 38, 41, 51, 81, 101, 1 11 , 128, 138, 141)-13-(111-benzimidazol-2-yl-thio-methyl)-11-[[3,4,6 -Trideoxy-3-(dimethylamino)-β-indole-hexyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
194) (2R,3S,4 ,5R,8 , 1 OR, 1 1 R, 12S， 13 S， 14R)- 11 -[[3 ,4,6- =脱氧 -3- (二甲基氨基) -β-D-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-(4-羟基-苯基-硫基-甲基) -3,5，8，10,12，14- 六甲基 -1 -氧-杂 -6-氮杂环十五垸 -15-酮；  194) (2R,3S,4,5R,8,1 OR, 1 1 R, 12S, 13 S, 14R)- 11 -[[3,4,6- =deoxy-3-(dimethylamino)- β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(4-hydroxy-phenyl-thio-methyl)-3, 5,8,10,12,14-hexamethyl-1 -oxo-hetero-6-azacyclopentadecane-15-one;
195) (21，38,41，51，81，101，1 111,128，138，1411)-13-[(烯丙基-硫基）-甲基]-1 1-[[3,4，6-三脱氧  195) (21, 38, 41, 51, 81, 101, 1 111, 128, 138, 1411)-13-[(allyl-thio)-methyl]-1 1-[[3,4,6- Triphod
136  136
替换页 （细则第 26条） -3- (二甲基氨基) -β-D-己吡喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5,8，10,12，14-六 甲基小氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) -3- (Dimethylamino)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12 , 14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
196) (21，38,41，51 ,811，101，111 ,128，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-(5-硫醇-戊基-硫基-甲基) -3，5,8,10，12，14- 六甲基小氧-杂 _6_氮杂环十五垸 _15_酮； 196) (21,38,41,51,811,101,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0- Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(5-thiol-pentyl-thio-methyl)-3,5,8 , 10,12,14- hexamethyl small oxo - 6 heteroaryl _ _ azetidin fifteen embankment _1 _ 5-one;
197) 1^-{4-[(211，33,41，51，81，101，111，128,133,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5，8,10,12,14-六甲基 -15-酮小氧-杂 -6-氮杂环十 五浣 -13-基-甲基-硫基] -苯基 }-乙酰胺  197) 1^-{4-[(211,33,41,51,81,101,111,128,133,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-anthracene -0-hexylopyranosyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-15-one Oxy-hetero-6-azetidine heteropentadepin-13-yl-methyl-thio]-phenyl}-acetamide
198) (2R，3S,4R，5R,8R,10R,l lR，12S,13S，14R)-l l-[[3，4,6-三脱氧 -3- (二甲基氨基） -β-D-己吡 喃木糖基]氧基] -2-乙基 -3,4，10，13-四羟基 -13-(6-硫醇-己基-硫基-甲基) -3,5,8，10,12，14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  198) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(6-thiol-hexyl-thio-methyl)-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
199) (2!，38，41，511,81 ,10] ,111^128,138,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基）^-0-己吡 喃木糖基]氧基 ]-2-乙基 -3，4，10，13-四羟基 -13-(8-硫醇 -正庚基-硫基-甲 基) -3,5，8，10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  199) (2!,38,41,511,81,10] ,111^128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)^-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(8-thiol-n-heptyl-thio-methyl)-3,5,8 , 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
200) (21，38，41 ,51 ,81 ,101，1111，128，138，141 )-1 [[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -13- (吡啶 -2-基-硫基- 甲基) -1-氧-杂 -6-氮杂环十五垸 -15-酮；  200) (21,38,41,51,81,101,1111,128,138,141 )-1 [[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- (pyridin-2-yl) -thio-methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
201) (21，33，41，5] ,81，1011，111 ,128,138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3，4,10，13-四羟基 -3，5，8,10，12,14-六甲基 -13- (壬基-硫基) -甲基 小氧-杂 -6-氮杂环十五垸 -15-酮；  201) (21,33,41,5] ,81,1011,111 ,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(mercapto-thio -methyloxy-hetero-6-nitrohecyclopentadecane-15-one;
202) (2R，3S,4R，5R，8R，10R,UR,12S，13S,14R)-1 [[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡喃木 糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-((6-轻基-己基-硫基)甲基) -3，5,8，10，12,14-六甲基小 氧-杂 -6-氮杂环十五烷 -15-酮  202) (2R, 3S, 4R, 5R, 8R, 10R, UR, 12S, 13S, 14R)-1 [[3,4,6-Trideoxy-3-(dimethylamino)-β-D-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-((6-light-hexyl-thio)methyl)-3,5,8, 10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one
203) (211,38，411,51，81，101，111，128，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）^-0-己吡 喃木糖基]氧基] -2-乙基 -3，4，10,13-四羟基 -3，5，8，10，12，14-六甲基 -13-正庚基 -硫基 -甲基 1-氧-杂 -6-氮杂环十五垸 -15-酮；  203) (211,38,411,51,81,101,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)^-0-hexyl Pyranopyranyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-n-heptyl-thio -methyl 1-oxo-hetero-6-azacyclopentadecane-15-one;
204) (21 ,38,4]，511,81 ,101，111，128,138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5，8，10，12，14-六甲基 -13-(2-甲基 -丁基 -硫基 -甲基 )-1-氧-杂 -6-氮杂环十五垸 -15-酮；  204) (21,38,4],511,81,101,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexanpyran Xylose]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(2-methyl-butyl -thio-methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
205) (21，38，41 ,51，81，101，111 ,128，138,141 )-13-(2，4-二氟-苯基-硫基-甲基）-1 [[3,4,6-三 脱氧 -3-(二甲基氨基）-β-ϋ-己吡喃木糖基]氧基 ]-2-乙基 -3,4,10,13-四羟基 -3，5，8,10，12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  205) (21, 38, 41, 51, 81, 101, 111, 128, 138, 141)-13-(2,4-difluoro-phenyl-thio-methyl)-1 [[3,4,6 -triptylo-3-(dimethylamino)-β-indole-hexyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8, 10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
206) (21 ,38,41{_,51 ,81 ,101 ,111 ,123，138，141 )-11-[[3，4,6-三脱氧-3-(二甲基氨基）-3-0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3，5，8，10,12,14-六甲基 -13- (吡啶 -2-基-甲基- 硫基-甲基) -1-氧-杂 -6-氮杂环十五垸 -15-酮；  206) (21,38,41{_,51 ,81 ,101 ,111 ,123,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3- 0-Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- (pyridine- 2-yl-methyl-thio-methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
207) (21，38，41 ,51 ,81 ,101^,1111,128,138,1411)-11-[[3，4，6-三脱氧-3-(二甲基氨基）-3-0-己吡 喃木糖基]氧基 ]-13-(1,2-二甲基-丙 ¾ -硫基 -甲基）-2-乙基 -3,4，10，13-四羟基  207) (21,38,41,51,81,101^,1111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexyl Pyranopyranyl]oxy]-13-(1,2-dimethyl-propanyl 3⁄4-thio-methyl)-2-ethyl-3,4,10,13-tetrahydroxy
137  137
替换页 （细则第 26条） -3，5，8，10，12,14-六甲基小氧-杂 -6-氮杂环十五垸 -15-酮； Replacement page (Article 26) -3,5,8,10,12,14-hexamethyloxy-hetero-6-azacyclopentadecane-15-one;
208) (211，38,41，51 ,81，1011,111，128，138，141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基] -2-乙基 -3,4,10，13-四羟基 -3,5，8,10，12,14-六甲基 -13-(1-甲基 -丁基 -硫基 -甲基 )-1-氧-杂 -6-氮杂环十五烷 -15-酮；  208) (211,38,41,51,81,1011,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexididine Iso-xylyloxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13-(1-methyl-butyl Base-thio-methyl)-1-oxo-hetero-6-azacyclopentadecane-15-one;
209) (2 ,38，41，51，811,101，1111,128,138，14]1)-11-[[3,4，6-三脱氧-3-(二甲基氨基)-3-0-己吡 喃木糖基]氧基 ]-2-乙基 -13- (乙基-硫基）甲基 -3,4，10，13-四羟基 -3,5,8,10,12,14-六甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  209) (2,38,41,51,811,101,1111,128,138,14]1)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-3-0-hexpyridinium Iso-xylyloxy]-2-ethyl-13-(ethyl-thio)methyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-six Methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
210) (2R,3S,4R,5R,8R,10R,11R，12S,13S，14R)-11-[[3，4,6-三脱氧 -3- (二甲基氨基） -β-D-己吡 喃木糖基]氧基] -2-乙基 -13- (甲基-硫基）甲基 -3，4，10，13-四羟基 -3,5,8，10，12，14-六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  210) (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D- Hexylpyranosyl]oxy]-2-ethyl-13-(methyl-thio)methyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14 - hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
211) (2R，3 S,4R，5R,8R， 10R,11R,12S,13S,14R)- 11 -[[3，4,6-三脱氧 -3 - (二甲基氨基） -β-D-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10,12,14-六甲基 -13- (邻-甲苯-硫基）甲 基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  211) (2R,3 S,4R,5R,8R,10R,11R,12S,13S,14R)- 11 -[[3,4,6-Trideoxy-3 - (dimethylamino)-β-D -Hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10,12,14-hexamethyl-13- (o-toluene -thio)methyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
212) (2R,3S，4R,5R，8R，10R，l lR，12S，13S,14R)-n-[[3,4,6-三脱氧 -3- (二甲基氨基） -β-D-己吡 喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -13-(4-硫醇-戊基-硫基-甲基) -3,5,8，10,12，14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮  212) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-n-[[3,4,6-Trideoxy-3-(dimethylamino)-β-D -hexylopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-13-(4-thiol-pentyl-thio-methyl)-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one
213) (21 ,38,41，51 ,81，1011,111，128，138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基）-卩-0-己吡 喃木糖基]氧基] -2-乙基 -13-(3，4-二氟-苯基-硫基-甲基) -3,4,10,13-四羟基 -3，5,8，10，12,14- 六甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  213) (21,38,41,51,81,1011,111,128,138,141 )-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexidyl Iso-xylyl]oxy]-2-ethyl-13-(3,4-difluoro-phenyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8 ,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
214) (2R,3S，4R，5R，8R,10R，l lR,12S，13S,14R)-l l-[[3,4,6-三脱氧 -3- (二甲基氨基) -β-D-己吡 喃木糖基]氧基] -2-乙基 -13-(3-氟-苯基-硫基-甲基) -3,4,10,13-四羟基 -3,5,8，10，12,14-六 甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  214) (2R,3S,4R,5R,8R,10R,l lR,12S,13S,14R)-l l-[[3,4,6-Trideoxy-3-(dimethylamino)-β- D-Hexylpyranosyl]oxy]-2-ethyl-13-(3-fluoro-phenyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5, 8,10,12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
215) (21，38,41，511,81，1011,1111,128,138，1411)-11-[[3，4,6-三脱氧-3-(二甲基氨基) -0-己吡 喃木糖基]氧基] -2-乙基 -13-(4-氟-苄基-硫基-甲基) -3，4，10，13-四羟基 -3,5,8,10,12,14-六 甲基 -1-氧-杂 -6-氮杂环十五烷 -15-酮；  215) (21,38,41,511,81,1011,1111,128,138,1411)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-0-hexyranium Glycosyl]oxy]-2-ethyl-13-(4-fluoro-benzyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
216) (211,38,41 ,51，81 ,101 ,111 ,128,138,141 )-11-[[3，4，6-三脱氧-3-(二甲基氨基)-卩-0-己吡 喃木糖基]氧基] -2-乙基 -13-(2-氟-苄基-硫基-甲基) -3，4，10，13-四羟基 -3，5，8，10,12，14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  216) (211,38,41,51,81,101,111,128,138,141)-11-[[3,4,6-Trideoxy-3-(dimethylamino)-oxime-0-hexpyran Glycosyl]oxy]-2-ethyl-13-(2-fluoro-benzyl-thio-methyl)-3,4,10,13-tetrahydroxy-3,5,8,10,12, 14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
217) (21 ,38，411,511,81 ,101，111，128，138，141 )-13-(4-氯-苄基-硫基-甲基)-1 [[3，4，6-三脱氧 -3- (二甲基氨基;) -β-D-己吡喃木糖基]氧基] -2-乙基 -3,4,10,13-四羟基 -3,5,8,10，12，14-六 甲基 -1-氧-杂 -6-氮杂环十五垸 -15-酮；  217) (21,38,411,511,81,101,111,128,138,141)-13-(4-chloro-benzyl-thio-methyl)-1 [[3,4,6-trideoxy -3- (dimethylamino;)-β-D-hexylpyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,8,10, 12,14-hexamethyl-1-oxo-hetero-6-azacyclopentadecane-15-one;
14. 一种根据权利要求 1~13任意一项所述化合物的药学上可接受的盐， 其特征在于， 所 述化合物的药学上可接受的盐为所述化合物与酸反应生成的，其中所述酸为无机酸或有机酸。  A pharmaceutically acceptable salt of a compound according to any one of claims 1 to 13, wherein a pharmaceutically acceptable salt of the compound is formed by reacting the compound with an acid, wherein The acid is an inorganic acid or an organic acid.
15. 根据权利要求 1-13任意一项所述的化合物或权利要求 14所述的药学上可接受的盐在 制备治疗哺乳动物、 鱼或鸟的细菌感染或原生动物感染的药物中的用途。  Use of a compound according to any one of claims 1 to 13 or a pharmaceutically acceptable salt according to claim 14 for the manufacture of a medicament for the treatment of a bacterial infection or protozoal infection of a mammal, fish or bird.
16. 一种组合物， 其特征在于， 其包含权利要求 1-13中任意一项所述的化合物或权利要 求 14所述的药学上可接受的盐， 以及药学上可以接受的载体。  A composition comprising the compound according to any one of claims 1 to 13 or the pharmaceutically acceptable salt according to claim 14, and a pharmaceutically acceptable carrier.
138  138
替换页 （细则第 26条）  Replacement page (Article 26)
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