CN116348474A

CN116348474A - Azoline saccharide compound, preparation method and application thereof

Info

Publication number: CN116348474A
Application number: CN202180069606.9A
Authority: CN
Inventors: 朱维良; 李波; 董三峰; 赵亦天; 贾琦; 张勇; 徐志建; 陈凯先
Original assignee: Shanghai Institute of Materia Medica of CAS
Current assignee: Shanghai Institute of Materia Medica of CAS
Priority date: 2020-10-15
Filing date: 2021-10-15
Publication date: 2023-06-27
Also published as: WO2022078487A1; CN114369125A

Abstract

The invention provides an oxazoline sugar (azoline) compound shown as a formula (I), a preparation method and application thereof, wherein the definition of each substituent is as described in the specification. The oxazoline saccharide compound has application prospect in the aspects of asymmetric synthesis of complex molecules, site selective modification of saccharide rings, mobility assembly of oligosaccharides and glycopeptides, specific glycosylation modification of peptides and proteins and the like, and provides a set of novel oxazoline saccharide-based synthesis tool kit for research of pharmaceutical chemistry or chemical biology.

Description

Azoline saccharide compound, preparation method and application thereof

Technical Field

The invention relates to the fields of organic chemistry, pharmaceutical chemistry, biological analysis, chemical biology and pharmacotherapeutics, in particular to an oxazoline sugar (azoline) compound, a pharmaceutical composition, a preparation method and application of the oxazoline sugar (azoline sugar) compound as a synthetic intermediate.

Background

Sugars and glycosides are widely found in glycoproteins and glycopeptides, natural products and drug molecules, for example as shown in the formulae below.

The chemical synthesis of saccharides is an important way to obtain saccharide compounds to study their physiological functions. And the characteristic glycopeptides can be obtained through the chemical modification of sugar to study the functions of glycoprotein; sugar rings of natural products and drug molecules can be modified to obtain analog development new drugs.

At present, the synthesis of sugar (glycoside) and the chemical modification of sugar ring are realized mainly through a complex hydroxyl selective protection process, and the method has the advantages of multiple steps and low efficiency. There is a lack of a simple, efficient synthetic method that allows for flexible multi-site modification of the sugar ring while simultaneously obtaining substrates that are amenable to glycosylation reactions.

The oligopeptide and polypeptide molecules not only exist in human bodies and play a key physiological role, but also many polypeptide drugs are widely applied to clinic and maintain the physical health of people. Peptide molecules, although highly active, are easily degraded, have a short half-life in vivo, and are easily destroyed by oral administration. Thus, chemical modification of peptide molecules is an important way to improve their in vivo stability and achieve oral administration.

Proteins are important targets for drug research, wherein the discussion of the relationship between the structure and the function of proteins is the basis for developing drug design, and the method of protein chemical modification is a common means for researching the relationship, but the current method of protein chemical modification has a great limitation, wherein the lack of specific chemical modification reagents is a main problem. Therefore, chemical modification reagents and methods are developed that can be used to selectively modify specific amino acid residues of proteins in physiological environments, and can be applied to drug discovery and design studies as well as chemical biology studies.

Li Bo and the like during the research of structural optimization design and synthesis of Berberine (Berberine) as a Chinese medicine active ingredient (Eur.J.Med. Chem.,2013,70,677-684), a novel acetal rearrangement reaction (Eur.J.Med. Chem.,2014,77,204-210) is discovered accidentally. In light of this, a method was developed for cyclizing a cyano compound with a glycolaldehyde dimethyl acetal compound in the presence of an acid to construct 4-methoxy oxazolines (Synthesis 2016,48,1331-1343). Based on this, the present inventors have further completed the following summary of the present invention.

Disclosure of Invention

The invention develops a novel oxazoline sugar compound, wherein the oxazoline unsaturated sugar compound can be conveniently converted into alpha, beta unsaturated ketone, and can directly perform selective halogenation reaction with a halogenating reagent, thereby realizing selective modification of sugar ring 2 position, 3 position and 4 position; the oxazoline saturated saccharide compound can obtain a 1-amino saccharide compound with 2-site selective ester group protection through simple conversion, and is used for constructing N-glycoside of 1, 2-site cis-glycosidic bond; the selective modification of the 3-position of the sugar ring can be simply realized, and a 1-amino sugar building block with the selective modification of the 2, 3-position can be further obtained; in addition, the amino group at the 1-position of the sugar ring can be conveniently converted into hydroxyl, so that the conversion from 1-amino sugar to 1-hydroxyl sugar is realized; in addition, the oxazoline saccharide compound has excellent oxazoline chiral group and can be directly used for asymmetric synthesis to construct complex chiral molecules.

The inventor of the present application has found through further research that the above-developed oxazoline unsaturated saccharide compound can perform a specific coupling reaction with the sulfhydryl group of the cysteine residue of the peptide molecule under physiological conditions, and other sensitive groups such as primary amino, secondary amino, amido, alcoholic hydroxyl, phenolic hydroxyl, disulfide bond, carboxyl and the like do not influence the coupling reaction, so that the oxazoline unsaturated saccharide compound can be used for specific glycosylation modification of peptide or protein.

In summary, the application provides an oxazoline sugar compound with a novel structure and a preparation method thereof, and develops a set of synthesis method, which can be applied to asymmetric synthesis of complex molecules, site selective modification of sugar rings, mobility assembly of oligosaccharides and glycopeptides, and specific glycosylation modification of peptides or proteins, thereby providing a set of synthesis tool kit based on novel oxazoline sugar for research of pharmaceutical chemistry or chemical biology.

An object of the present invention is to provide an oxazoline saccharide compound represented by formula I or a pharmaceutically acceptable salt thereof.

It is another object of the present invention to provide a process for the preparation of the oxazoline saccharide compound of formula I.

It is a further object of the present invention to provide the use of the oxazoline saccharide compound of formula I as a synthetic intermediate.

It is a further object of the present invention to provide compounds of formula IV, formula V, formula VI or pharmaceutically acceptable salts thereof, prepared from compounds of formula I.

According to one aspect of the present invention there is provided an oxazoline saccharide compound represented by formula I:

wherein,

is a double bond or a single bond;

n is 0 or 1, in particular 1;

R ¹ 1 or 2 substituents on the A ring selected from unsubstituted or hydroxy, C1-C6 alkanoyloxy, C6-C12 aralkoxy or C6-C12 aryloxy substituted C1-C6 alkyl, unsubstituted or C1-C6 alkyl substituted C1-C6 alkanoyloxy, unsubstituted or C6-C12 aryl substituted C1-C6 alkoxy, unsubstituted or C1-C6 alkyl substituted C6-C12 aryloxy, unsubstituted or C1-C6 alkyl substituted C6-C12 aralkoxy, hydroxy, monoglycosyloxy, disaccharideyloxy, oligosaccharyloxy, polysaccharyloxy, hydrogen; preferably, R ¹ 1 or 2 substituents on the A ring selected from unsubstituted or hydroxy, C1-C6 alkanoyloxy, C6-C12 aryloxy or C6-C12 aryloxy substituted C1-C3 alkyl (in particular unsubstituted or hydroxy, C1-C3 alkanoyloxy or C6-C12 aryloxy substituted C1-C3 alkyl), unsubstituted or C1-C3 alkyl substituted C1-C3 alkanoyloxy, unsubstituted or C6-C12 aryl substituted C1-C3 alkoxy, unsubstituted or C1-C3 alkyl substituted C6-C12 aryloxy, unsubstituted or C1-C3 alkyl substituted C6-C12 aralkoxy, hydroxy, monoglycosyloxy, disaccharideyloxy, hydrogen; more preferably, R ¹ Is 1 or 2 substituents on the A ring selected from the group consisting of C1-C3 alkyl, benzyloxy C1-C3 alkyl, hydroxy C1-C3 alkyl, C1-C6 alkanoyloxy C1-C3 alkyl (especially C1-C3 alkanoyloxy C1-C3 alkyl), C6-C12 aralkoxy C1-C3 alkyl, C1-C3 alkyl C1-C3 alkanoyloxy, C1-C3 alkoxy, C6-C12 aryloxy, C6-C12 aralkoxy, hydroxy, monoglycosyloxy, disaccharideA acyloxy group, a benzyloxy group, and hydrogen;

R ² a 5-to 9-membered heteroaryl group selected from C1-C6 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted C6-C12 aryl, wherein the substituent of C6-C12 aryl is a 1, 2, 3 or 4 substituent selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, halogenated C1-C6 alkyl, C1-C6 alkanoyl, C2-C6 alkynyl, phenyl, or two adjacent substituents on C6-C12 aryl together with the attached aryl carbon atom form a 5-to 9-membered heterocyclyl group, the substituent of a 5-to 9-membered heteroaryl group being halogen; preferably, 1, 2, 3 or 4 substituents selected from C1-C6 alkyl, C3-C6 cycloalkyl, naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-9 membered heteroaryl, wherein the phenyl substituent is selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, halogenated C1-C3 alkyl, C1-C6 alkanoyl, C2-C6 alkynyl, phenyl, or two adjacent substituents on phenyl together with the attached phenyl carbon atom form a 5-9 membered heterocyclyl, the 5-9 membered heteroaryl substituent is halogen; more preferably, R ² A substituent selected from the group consisting of C1-C3 alkyl, C3-C5 cycloalkyl, naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-to 9-membered heteroaryl, wherein the substituent for phenyl is 1, 2, 3 or 4 substituents selected from the group consisting of C1-C3 alkyl, C1-C3 alkoxy, halogen, trifluoromethyl, C1-C3 alkanoyl, C2-C4 alkynyl, phenyl, or two adjacent substituents on phenyl together with the attached phenyl carbon atom form dioxolane, and the substituent for 5-to 9-membered heteroaryl is selected from F, cl, br, I;

R ³ selected from the group consisting of hydrogen, C1-C6 alkanoyloxy, C1-C6 alkyl substituted or unsubstituted C6-C12 aralkyloxy, C1-C6 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C6 alkoxy, hydroxy, monoglycosyloxy, disaccharideyloxy, oligosaccharyloxy, polysaccharide yloxy; preferably, hydrogen, C1-C6 alkanoyloxy (in particular C1-C3 alkanoyloxy), C1-C3 alkyl-substituted or unsubstituted C6-C12 aryloxy, C1-C6 alkoxy (in particular C1-C3 alkoxy), C6-C12 aralkoxy; more preferably, R ³ Selected from hydrogen, C1-C6 alkanoyloxy (in particular C1-C3 alkanoyloxy)) C1-C6 alkoxy (in particular C1-C3 alkoxy), C6-C12 aralkyloxy;

R ⁴ Selected from hydrogen, hydroxy, C1-C6 alkanoyloxy, C1-C6 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C6 alkoxy; preferably, hydrogen, hydroxy, C1-C6 alkanoyloxy (especially C1-C3 alkanoyloxy), C1-C3 alkyl substituted or unsubstituted C6-C12 aralkoxy, C1-C3 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C3 alkoxy; preferably, R ⁴ Selected from hydrogen, hydroxy, C1-C6 alkanoyloxy (especially C1-C3 alkanoyloxy), C1-C3 alkoxy, C6-C12 aralkyloxy;

q is O, N or S, in particular O;

w is O, N or S, in particular O.

In particular, R ¹ Is 1 or 2 substituents on the A ring selected from the group consisting of acetoxymethyl, pentanoyloxymethyl, benzoyloxymethyl, benzyloxymethyl, acetoxy, pentanoyloxy, benzoyloxy, methyl, ethyl, hydroxy, hydroxymethyl, monoglycosyloxy, disaccharideyloxy, benzyloxy and hydrogen.

In particular, R ² Selected from methyl, ethyl, naphthyl, substituted or unsubstituted phenyl, and substituted or unsubstituted 5-9 membered heteroaryl, wherein the phenyl is substituted with 1, 2, 3, or 4 substituents selected from methyl, ethyl, methoxy, ethoxy, F, cl, br, I, trifluoromethyl, acetyl, ethynyl, phenyl, or two adjacent substituents on phenyl together with the attached phenyl carbon atom form dioxolane, and the 5-9 membered heteroaryl is selected from thienyl and furyl, the substituents of which are selected from F, cl, br, I.

In particular, R ³ Selected from the group consisting of hydrogen, acetoxy, pentanoyloxy, benzoyloxy and benzyloxy.

In particular, R ⁴ Selected from the group consisting of hydrogen, hydroxy, acetoxy, pentanoyloxy, benzoyloxy, and benzyloxy.

In particular, the compounds of formula I above may be of formula II or III below

Wherein n, R ¹ ，R ² ，R ³ ，R ⁴ W and Q are as defined above.

In this context, the term "a" is used herein,

C1-C6 alkyl means a straight-chain or branched saturated alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, tert-butyl.

C2-C6 alkynyl refers to alkynyl having a carbon-carbon triple bond of 2 to 6 carbon atoms, for example, ethynyl, 2-propynyl.

C1-C6 alkanoyloxy means R-C (=O) O-wherein R is C1-C6 alkyl, as defined above, for example formyloxy, acetoxy.

C1-C6 alkanoyl refers to R-C (=O) -, where R is C1-C6 alkyl, as defined above, and may be, for example, acetyl, propionyl.

C6-C12 aryl refers to a monocyclic aromatic group having 6 to 14 carbon atoms or a condensed or unfused polycyclic aromatic group, in the case of a multicyclic ring, as long as one of the carbocycles is an aromatic ring, such as phenyl, benzyl, naphthyl.

C6-C12 aryloxy means RO-, wherein R is a C6-C12 aryl group, which may be, for example, phenoxy, benzyloxy.

C1-C6 alkoxy means RO-, wherein R is C1-C6 alkyl, as defined above, and may be methoxy, ethoxy, propoxy, for example.

C6-C12-aralkyloxy means R-C (=O) O-, wherein R is C6-C12-aryl, as defined above, for example benzoyloxy.

C6-C12 aroyl refers to R-C (=O) -, where R is C6-C12 aryl, as defined above, and may be, for example, benzoyl, phenylacetyl.

The monosaccharide oxygroup means RO-, wherein R is a monosaccharide group, and the monosaccharide group means a sugar having 3 to 6 carbon atoms in the molecular structure, such as glyceraldehyde of a tricarbon sugar; erythrose, su Litang, four carbon sugars; arabinose, ribose, xylose, lyxose of five-carbon sugar; glucose, mannose, fructose, galactose of six carbon sugars.

Disaccharide oxygroup means RO-, wherein R is a disaccharide group, which may be, for example, maltose, lactose, sucrose, trehalose, gentiobiose.

Oligosaccharyl oxy refers to RO-, wherein R is oligosaccharyl, which may be e.g. malto-oligosaccharide, cyclodextrin, fructo-oligosaccharide, soy-oligosaccharide.

Polysaccharide-based oxy groups refer to RO-, wherein R is a polysaccharide-based group, which may be, for example, starch, cellulose and glycogen, inulin.

C3-C6 cycloalkyl means a saturated monocyclic hydrocarbon radical having 3 to 8 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl.

A5-to 9-membered heterocyclic group means a non-aromatic ring group having 5 to 9 ring atoms in the ring and containing 1 to 4 hetero atoms, and a hetero atom means nitrogen, oxygen or sulfur, for example, azetidinyl, pyrrolidinyl, pyrrolinyl, tetrahydrofuranyl, dihydrofuranyl, piperazinyl, piperidinyl, morpholinyl, dioxolan.

A 5-9 membered heteroaryl group refers to a monocyclic or polycyclic aromatic ring group having 5-9 ring atoms which contains 1-4 heteroatoms in the ring, the heteroatoms referring to nitrogen, oxygen or sulfur, for example pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, pyridinyl, pyrimidinyl, furanyl, thienyl, isoxazolyl, indolyl.

Halogen refers to F, cl, br, I.

Halogenated C1-C6 alkyl refers to halogen substituted C1-C6 alkyl, such as trifluoromethyl, trichloromethyl, difluoromethyl, difluoromethylene.

Herein, the expression "a-group B group" means that the B group is a group attached to the parent nucleus, which is substituted with an a group. For example, C1-C3 alkanoyloxy C1-C3 alkyl means that the C1-C3 alkyl attached to the parent nucleus is substituted with C1-C3 alkanoyloxy; for example, acetoxymethyl represents that the methyl group attached to the parent nucleus is substituted with acetoxy.

Specifically, the compounds of formula I are shown below:

according to another aspect of the present invention, there is provided a process for preparing an oxazoline saccharide compound represented by formula I: the compound 1 and the compound 2 are in a solvent S to generate the compound shown in the formula I under the action of A

Specifically, the method includes the following methods shown in route two and route three:

wherein n, R ¹ ，R ² ，R ³ ，R ⁴ W and Q are as defined above, R ⁵ And R is ⁶ Selected from the group consisting of substituted or unsubstituted C1-C6 alkanoyl, substituted or unsubstituted C6-C12 aroyl, substituted or unsubstituted C6-C12 aryl, and C1-C6 alkyl, wherein the substituents for substitution are selected from the group consisting of halogen, C1-C6 alkyl, and C1-C6 alkoxy; u is as defined for W.

As shown in scheme two, compound 1 and compound 2 in solvent S1 in the presence of A1 to form compound II;

as shown in scheme three, compound 1 and compound 2 in solvent S2 in the presence of A2 to form compound III;

wherein A, A and A2 are lewis acids, protic acids, or a combination of lewis acids and protic acids;

wherein S, S and S2 are aprotic solvents, protic solvents, or a combination of aprotic and protic solvents;

the lewis acid is preferably one or more selected from metal halides such as ferric chloride, zinc dichloride, aluminum trichloride, ruthenium trichloride, niobium pentachloride, antimony pentafluoride and the like, and trifluoromethanesulfonates such as silver trifluoromethanesulfonate, indium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, ytterbium trifluoromethanesulfonate, copper trifluoromethanesulfonate and the like;

The protonic acid is preferably one or more common protonic acids selected from hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid and the like;

preferably, A1 is a protic acid, more preferably trifluoromethanesulfonic acid;

a2 is a protic acid, more preferably trifluoromethanesulfonic acid.

The aprotic solvents include, but are not limited to, toluene, acetone, methylene chloride, 1, 2-dichloroethane, tetrahydrofuran, acetonitrile, xylene, chlorobenzene, dioxane, dimethyl sulfoxide, dimethylformamide, dimethylacetamide;

the protic solvents include, but are not limited to, n-butanol, n-propanol, ethanol, methanol, glycerol, ethylene glycol, water;

preferably, S1 is a combination of dichloromethane and water or a combination of dichloroethane and water;

s2 is dichloromethane or dichloroethane.

According to another aspect of the present invention there is provided the use of an oxazoline saccharide compound (compounds of formulae II and III) as shown in formula I for specific modification of different sites on the saccharide ring (route four, route five), for the flexible assembly of oligosaccharides and glycopeptides (route four); and for the detection of thiol-containing molecules and the specific modification of thiols of peptides and proteins (scheme six).

According to the use of the present invention as described above, the use comprises a method for synthesizing the following compounds of formula IV, formula V and formula VI from an oxazoline saccharide compound (compounds of formula II and formula III) as shown in formula I, the method comprising the following route four, route five, route six:

after the compound II reacts with acid, a compound IV with R8 being hydrogen is generated, and then the compound IV with carboxylic acid, anhydride, acyl chloride, boric acid compound or halogenated compound is reacted to be converted into a compound IV with R8 being not hydrogen;

wherein n, R ¹ ，R ² ，R ³ W and Q are as defined above, R ⁸ Is hydrogen, p-tolyl, 1-carboxyethyl-4-carbonyl, p-methoxyphenylcarbonyl, methyl 2- (tert-butoxycarbonylamino) pentanoate 4-carbonyl, p-methylphenylboronic acid.

In a method of synthesizing a compound of formula IV, the acid includes, but is not limited to, a protic acid, a lewis acid, or a combination thereof, wherein the protic acid and lewis acid are each as defined above;

when X is hydrogen, compound V can be obtained from compound III by reaction with water in the presence of an acid (scheme five);

when X is halogen, compound V is obtainable by reacting compound III with a halogenating agent (scheme five);

wherein R is ¹ ，R ² ，R ³ ，R ⁴ ，R ⁵ ，R ⁶ W and Q are as defined above, and X is hydrogen or halogen.

In the synthetic method of the compound of formula V, the halogenating reagent includes, but is not limited to, N bromosuccinimide, iodine monochloride, and the like;

in another aspect, the invention provides a method of synthesizing a compound of formula VI, comprising, as shown in scheme six,

reacting the compound III with a sulfhydryl compound to convert the compound III into a compound VI;

wherein R is ¹ ，R ² ，R ⁴ W and Q are as defined above, R ⁷ Selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C12 aryl, cysteine residue containing oligopeptides or polypeptides or proteins, wherein the substituents for substitution are selected from halogen, C1-C6 alkyl, C1-C6 alkoxy.

In the method of synthesizing the compound of formula VI, the thiol-containing compound includes, but is not limited to, thiols, cysteines, and oligopeptides, polypeptides, proteins, etc. that contain cysteine structures.

According to a further aspect of the present invention there is provided a compound prepared from a compound of formula I:

wherein n, R ¹ ，R ² ，R ³ W and Q are as defined above; r is R ⁷ Selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C12 aryl, cysteine residue-containing oligopeptides or polypeptides or proteins, wherein the substituents for substitution are selected from halogen, C1-C6 alkyl, C1-C6 alkoxy; r is R ⁸ Is hydrogen, p-tolyl, 1-carboxyethyl-4-carbonyl, p-methoxyphenylcarbonyl, methyl 2- (tert-butoxycarbonylamino) valerate 4-carbonyl, X is hydrogen or halogen.

In particular, the compounds prepared from the compounds of formula I are selected from:

Advantageous effects

the invention designs and synthesizes the oxazoline sugar compound, has novel structure, can be used for synthesizing intermediates of medicines, and realizes asymmetric synthesis of complex molecules; specific modification of different sites on the sugar ring can be realized, and the mobility assembly of the oligosaccharide and the glycopeptide can be realized; the method can also be used for detecting thiol-containing molecules and specifically modifying the thiol of peptides or proteins, and has great scientific value and potential economic benefit.

Drawings

FIG. 1 is an X-ray single crystal diffraction pattern of II-4

FIG. 2 is an X-ray single crystal diffraction pattern of III-1

FIG. 3 is a mass spectrum of compound VI-2;

FIG. 4 is a mass spectrum of compound VI-3.

Detailed Description

The invention is further illustrated, but is not limited, by the following examples.

The preparation examples of the oxazoline sugar of the formula I are as follows:

the following are examples of the preparation of compounds of formula II:

example II-1 preparation of Compound II-1

beta-D-glucose pentaacetate (195 mg,0.5 mmol) was weighed, methylene chloride (10 ml) was added for dissolution, benzonitrile (50. Mu.l, 0.6 mmol) was added, water (11. Mu.l, 0.6 mmol) was added, and after stirring well, trifluoromethanesulfonic acid (106. Mu.l, 1.2 mmol) was slowly added to the reaction solution for 2 hours. After the completion of the reaction, deionized water (20 ml) was added to quench the reaction, and the reaction mixture was extracted twice with ethyl acetate (15 ml). The organic phases were then combined, washed once with deionized water (30 ml), once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate and filtered. After evaporating the organic phase under reduced pressure using a rotary evaporator, adding dichloromethane for redissolving, stirring with silica gel, and performing silica gel column chromatography PE: ea=2:1 elution gave 144.3mg of the product as a yellow oil in 74% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.05(m,2H),7.64–7.54(m,1H),7.48(m,2H),6.12(d,J＝7.7Hz,1H),5.33(t,J＝4.1Hz,1H),5.06–4.98(m,1H),4.66(m,1H),4.34(dd,J＝12.1,5.1Hz,1H),4.28–4.17(m,2H),2.18(s,3H),2.12(s,3H),1.97(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.68,169.53,169.47,166.59,132.68,128.90,128.59,126.22,93.24,75.83,70.56,68.08,67.30,63.28,20.88,20.79,20.62.HRMS(ESI)：C ₁₉ H ₂₂ NO ₈ [M+H] ⁺ Calculated value:392.134, found: 392.1351.

example II-2 preparation of Compound II-2

P-methoxybenzonitrile (66.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 123.1mg as yellow oil in 57% yield. ¹ H NMR(600MHz,CDCl ₃ )δ7.96(d,J＝8.6Hz,2H),6.94(d,J＝8.6Hz,2H),6.05(d,J＝7.6Hz,1H),5.29(dd,J＝5.2,2.9Hz,1H),5.02–4.94(m,1H),4.65–4.56(m,1H),4.30(dd,J＝12.2,5.0Hz,1H),4.17(m,2H),3.85(s,3H),2.15(s,3H),2.08(s,3H),1.94(s,3H). ¹³ C NMR(150MHz,CDCl ₃ ) δ170.59,169.45,169.38,166.30,163.05,130.68,113.85,93.11,75.61,70.49,67.78,67.23,63.18,55.36,20.79,20.70,20.55.HRMS(ESI)：C ₂₀ H ₂₄ NO ₉ [M+H] ⁺ Calculated values: 422.1446, found: 422.1449.

example II-3 preparation of Compound II-3

Methoxybenzonitrile (66.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 123.1mg as yellow oil in 57% yield. ¹ H NMR(600MHz,CDCl ₃ )δ7.60(m,1H),7.55(m,1H),7.36(m,1H),7.10(m,1H),6.08(d,J＝7.7Hz,1H),5.30(d,J＝4.1Hz,1H),4.98(m,1H),4.63(m,1H),4.31(m,1H),4.19(dd,J＝12.1,2.9Hz,1H),3.85(s,3H),3.75(m,1H),2.15(s,3H),2.09(s,3H),1.95(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.57,169.44,169.35,166.46,159.51,129.56,121.20,119.35,113.05,93.07,75.70,70.33,67.93,67.16,63.16,55.40,20.78,20.69,20.54.HRMS(ESI)：C ₂₀ H ₂₄ NO ₉ [M+H] ⁺ Calculated values: 422.1446, found: 422.1449.

example II-4 preparation of Compound II-4

Piperonyl cyanide (73.5 mg,0.5 mmol) and beta-D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give 135.5mg of the product as a yellow oil in 62% yield. ¹ H NMR(600MHz,CDCl ₃ )δ7.59(m,1H),7.46(s,1H),6.86(m,1H),6.08–6.01(m,3H),5.28(m,1H),5.00–4.93(m,1H),4.60(m,1H),4.31(dd,J＝12.2,5.0Hz,1H),4.22–4.15(m,2H),2.15(s,3H),2.09(s,3H),1.97(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.23,169.13,169.08,165.67,150.98,147.41,123.89,119.52,108.34,107.83,101.35,92.72,75.43,70.15,67.49,66.81,62.78,20.33,20.31,20.20.HRMS(ESI)：C ₂₀ H ₂₂ NO ₁₀ [M+H] ⁺ Calculated values: 436.1238, found: 436.1248.

the acetyl protecting group of the compound II-4 is removed by triethylamine/methanol to obtain a solid compound II-4', and the structure (shown in figure 1) is determined as follows by an X-ray single crystal diffraction experiment:

example II-5 preparation of Compound II-5

P-chlorobenzonitrile (68.5 mg,0.5 mmol) and beta-D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 57.5mg as yellow oil in 27% yield. ¹ H NMR(600MHz,CDCl ₃ )δ7.95(d,J＝8.6Hz,2H),7.46–7.39(m,2H),6.07(d,J＝7.7Hz,1H),5.30–5.24(m,1H),4.97(m,1H),4.63(m,1H),4.30(dd,J＝12.1,5.1Hz,1H),4.18(dd,J＝12.1,2.9Hz,1H),3.76–3.67(m,1H),2.15(s,3H),2.08(s,3H),1.94(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.54,169.36,165.53,138.98,130.09,128.86,124.56,93.15,75.97,70.44,68.11,67.05,63.08,20.76,20.68,20.52.HRMS(ESI)：C ₁₉ H ₂₁ ClNO ₈ [M+H] ⁺ Calculated values: 426.0950, found: 426.0955.

example II-6 preparation of Compound II-6

P-bromoxynil (90 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 51.7mg as yellow oil in 22% yield. ¹ H NMR(600MHz,CDCl ₃ )δ7.88(d,J＝8.5Hz,2H),7.60(d,J＝8.3Hz,2H),6.07(d,J＝7.7Hz,1H),5.28(dd,J＝9.7,5.4Hz,1H),5.01–4.95(m,1H),4.63(m,1H),4.30(dd,J＝12.1,5.1Hz,1H),4.18(dd,J＝12.1,2.8Hz,1H),3.73(m,1H),2.16(s,3H),2.09(s,3H),1.95(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.55,169.37,165.65,131.85,130.23,127.56,125.01,93.15,75.97,70.43,68.12,67.05,63.08,20.76,20.68,20.53.HRMS(ESI)：C ₁₉ H ₂₁ BrNO ₈ [M+H] ⁺ Calculated values: 470.0445, found: 470.0442.

example II-7 preparation of Compound II-7

P-trifluoromethylbenzonitrile (85.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give 48.3mg of the product as a yellow oil in 21% yield. ¹ H NMR(600MHz,CDCl ₃ )δ8.20–8.13(m,2H),7.75(d,J＝8.1Hz,2H),6.14(d,J＝7.8Hz,1H),5.32(m,1H),5.01(m,1H),4.70(m,1H),4.33(dd,J＝12.1,5.1Hz,1H),4.21(dd,J＝12.2,2.9Hz,1H),3.79–3.72(m,1H),2.19(s,3H),2.11(s,3H),1.98(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.67,169.50,169.48,165.27,129.30,125.64,125.61,93.25,76.25,70.51,68.34,67.11,63.14,20.88,20.80,20.64.HRMS(ESI)：C ₂₀ H ₂₁ F ₃ NO ₈ [M+H] ⁺ Calculated values: 460.1214, found: 460.1212.

example II-8 preparation of Compound II-8

Acetylbenzonitrile (72.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give 79.6mg total as yellow oily product in 35% yield. ¹ H NMR(600MHz,CDCl ₃ )δ8.14–8.08(m,2H),8.02(d,J＝8.7Hz,2H),6.11(d,J＝7.8Hz,1H),5.32–5.26(m,1H),4.98(m,1H),4.66(m,1H),4.31(dd,J＝12.2,5.1Hz,1H),4.19(dd,J＝12.1,2.9Hz,1H),3.74(m,1H),2.64(s,3H),2.16(s,3H),2.08(s,3H),1.94(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ197.20,170.54,169.36,165.48,139.90,130.03,129.03,128.30,128.27,93.18,76.03,70.40,68.27,67.00,63.06,26.73,20.76,20.68,20.52.HRMS(ESI)：C ₂₁ H ₂₄ NO ₉ [M+H] ⁺ Calculated values: 434.1446, found: 434.1453.

example II-9 preparation of Compound II-9

3,4, 5-methoxybenzonitrile (96.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 161.9mg as a clear oil with a yield of 67%. ¹ H NMR(500MHz,CDCl ₃ )δ7.27(s,2H),6.07(d,J＝7.6Hz,1H),5.34–5.29(m,1H),4.99(m,1H),4.62(m,1H),4.32 (dd,J＝12.1,4.9Hz,1H),4.19(dd,J＝12.1,2.9Hz,1H),3.91(d,J＝2.0Hz,9H),3.79–3.71(m,1H),2.16(s,3H),2.09(s,3H),1.97(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.23,169.06,165.99,152.72,141.51,120.69,105.64,92.71,75.60,70.05,67.43,66.89,62.75,60.54,55.90,29.25,20.45,20.36,20.23.HRMS(ESI)：C ₂₂ H ₂₈ NO ₁₁ [M+H] ⁺ Calculated values: 482.1657, found: 482.1662.

Example II-10 preparation of Compound II-10

Synthesis of 2-cyanofuran (46.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) as described for II-1 gave 131.5mg of the product as a yellow oil in 69% yield. ¹ H NMR(600MHz,CDCl ₃ )δ7.61(dd,J＝1.8,0.8Hz,1H),7.12(dd,J＝3.5,0.8Hz,1H),6.54(dd,J＝3.5,1.7Hz,1H),6.06(d,J＝7.6Hz,1H),5.27–5.23(m,1H),4.98–4.95(m,1H),4.59(ddd,J＝7.7,3.7,0.9Hz,1H),4.29(dd,J＝12.1,5.1Hz,1H),4.16(dd,J＝9.7,2.5Hz,1H),3.75(ddd,J＝8.2,5.1,2.8Hz,1H),2.13(s,3H),2.07(s,3H),1.96(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.55,169.40,169.28,158.24,146.55,146.48,146.35,141.42,116.92,111.90,92.96,75.69,70.40,67.93,67.04,63.00,20.73,20.66,20.51.HRMS(ESI)：C ₁₇ H ₂₀ NO ₉ [M+H] ⁺ Calculated values: 382.1133, found: 382.1143.

example II-11 preparation of Compound II-11

3-Cyanothiophene (54 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 106.7mg as a yellow oil in 56% yield. ¹ H NMR(600MHz,CDCl ₃ )δ8.05(dd,J＝3.0,1.2Hz,1H),7.58(dd,J＝5.1,1.2Hz,1H),7.38(dd,J＝5.1,3.0Hz,1H),6.06(d,J＝7.6Hz,1H),5.30–5.27(m,1H),5.00–4.95(m,1H),4.59(m,1H),4.31(dd,J＝12.1,5.0Hz,1H),4.22–4.15(m,2H),2.16(s,3H),2.09(s,3H),1.96(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.58,169.43,169.37,162.58,130.96,127.30,126.63,93.09,75.56,70.46,67.88,67.17,63.11,20.78,20.69,20.52.HRMS(ESI)：C ₁₇ H ₂₀ NO ₈ S[M+H] ⁺ Calculated values: 398.0904, found: 398.0917.

example II-12 preparation of Compound II-12

2-Chlorobenzonitrile (68.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 74.4mg as a clear oil with a yield of 35%.1H NMR (500 MHz, CDCl) ₃ )δ7.8(dd,J＝7.7,1.7Hz,1H),7.5–7.4(m,2H),7.4(td,J＝7.5,1.4Hz,1H),6.1(d,J＝7.8Hz,1H),5.3(t,J＝4.1Hz,1H),5.0(ddd,J＝8.7,4.5,0.9Hz,1H),4.6(ddd,J＝7.8,3.7,0.9Hz,1H),4.3(dd,J＝12.1,5.2Hz,1H),4.2(dd,J＝12.1,2.8Hz,1H),3.8(ddd,J＝8.4,5.2,2.8Hz,1H),2.2(s,3H),2.1(s,3H),2.0(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.2,169.1,168.9,164.7,133.5,132.2,131.2,130.6,126.2,125.4,93.0,70.1,67.6,66.8,62.7,59.9,20.4,20.3,20.2.HRMS(ESI)：C ₁₉ H ₂₁ ClNO ₈ [M+H] ⁺ Calculated values: 426.095, found: 426.0958.

example II-13 preparation of Compound II-13

2-bromoxynil (91.0 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 84.5mg as a clear oil with a yield of 38%. ¹ H NMR(600MHz,CDCl ₃ )δ7.8(dd,J＝7.6,1.9Hz,1H),7.7(dd,J＝7.9,1.3Hz,1H),7.4(dtd,J＝22.4,7.5,1.6Hz,2H),6.1(d,J＝7.8Hz,1H),5.3(t,J＝4.2Hz,1H),5.0(ddd,J＝8.8,4.6,0.8Hz,1H),4.7(ddd,J＝7.9,3.8,0.8Hz,1H),4.3(dd,J＝12.2,5.2Hz,1H),4.2(dd,J＝12.1,2.8Hz,1H),3.9(ddd,J＝8.3,5.2,2.7Hz,1H),2.2(s,3H),2.1(s,3H),2.0(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.7,169.6,169.4,165.8,134.3,132.7,131.7,128.0,127.3,122.2,93.4,75.9,70.7,68.1,67.4,63.2,20.9,20.8,20.7.HRMS(ESI)：C ₁₉ H ₂₁ BrNO ₈ [M+H] ⁺ Calculated values: 470.0455, found: 470.0457.

example II-14 preparation of Compound II-14

2-iodobenzonitrile (114.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 142.9mg as a clear oil in 56% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.0(dd,J＝8.0,1.2Hz,1H),7.8(dd,J＝7.7,1.7Hz,1H),7.5(td,J＝7.6,1.2Hz,1H),7.2(td,J＝7.7,1.7Hz,1H),6.2(d,J＝7.8Hz,1H),5.4(t,J＝4.1Hz,1H),5.0(ddd,J＝8.8,4.7,0.9Hz,1H),4.7(ddd,J＝7.8,3.7,0.9Hz,1H),4.4(dd,J＝12.1,5.2Hz,1H),4.3(dd,J＝12.2,2.8Hz,1H),3.9(ddd,J＝8.4,5.2,2.8Hz,1H),2.2(s,3H),2.1(s,3H),2.0(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.7,169.6,169.4,166.5,141.2,132.6,131.6,131.2,128.0,94.7,93.4,76.1,70.7,68.2,67.4,63.1,20.8,20.8,20.7.HRMS(ESI)：C ₁₉ H ₂₁ INO ₈ [M+H] ⁺ Calculated values: 518.0306, found: 518.0317.

example II-15 preparation of Compound II-15

2-chloro-3-methoxybenzonitrile (110.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 54.0mg as a clear oil with a yield of 24%. ¹ H NMR(600MHz,CDCl ₃ )δ7.38(dd,J＝7.8,1.4Hz,1H),7.31(t,J＝8.0Hz,1H),7.09(dd,J＝8.3,1.4Hz,1H),6.12(d,J＝7.8Hz,1H),5.33(t,J＝4.0Hz,1H),4.98(dd,J＝8.8,4.3Hz,1H),4.63(dd,J＝7.9,3.7Hz,1H),4.31(dd,J＝12.2,5.3Hz,1H),4.21(dd,J＝12.2,2.7Hz,1H),3.94(s,3H),3.84(s,1H),2.15(s,3H),2.09(s,3H),2.01(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.69,169.58,169.36,165.45,127.28,122.99,114.84,93.29,75.59,70.45,67.95,67.35,63.23,56.53,20.83,20.78,20.68.HRMS(ESI)：C ₂₀ H ₂₃ ClNO ₉ [M+H] ⁺ Calculated values: 456.1056, found: 456.1060.

EXAMPLE II-16 preparation of Compound II-16

2-bromo-3-methoxybenzonitrile (105.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 116.8mg as a clear oil with a yield of 47%. ¹ H NMR(500MHz,CDCl ₃ )δ7.36(t,J＝8.0Hz,1H),7.32–7.29(m,1H),7.05(dd,J＝8.1,1.6Hz,1H),6.12(d,J＝7.8Hz,1H),5.36(t,J＝4.0Hz,1H),4.99(m,1H),4.65(m,1H),4.32(dd,J＝12.1,5.3Hz,1H),4.22(dd,J＝12.1,2.7Hz,1H),3.93(d,J＝7.9Hz,4H),2.15(s,3H),2.09(s,3H),2.04(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.66,169.56,169.33,166.22,156.62,128.17,123.22, 114.52,93.28,75.96,70.70,68.00,67.42,63.15,60.34,56.61,20.78,20.73,20.66.HRMS(ESI)：C ₂₀ H ₂₃ BrNO ₉ [M+H] ⁺ Calculated values: 500.0551, found: 500.0556.

example II-17 preparation of Compound II-17

2-chloro-4-methoxybenzonitrile (83.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 151.2mg as a clear oil with a yield of 67%. ¹ H NMR(500MHz,CDCl ₃ )δ7.85(d,J＝8.8Hz,1H),7.04(d,J＝2.5Hz,1H),6.88(dd,J＝8.8,2.5Hz,1H),6.13(d,J＝7.7Hz,1H),5.37–5.31(m,1H),5.00(m,1H),4.61(m,1H),4.33(dd,J＝12.1,5.2Hz,1H),4.23(dd,J＝12.1,2.9Hz,1H),3.88(s,3H),3.83(m,1H),2.17(s,3H),2.11(s,3H),2.01(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.67,169.55,169.41,164.86,162.48,135.50,133.03,117.76,116.40,112.81,93.44,75.29,70.60,68.05,67.33,63.25,55.72,20.84,20.77,20.65.HRMS(ESI)：C ₂₀ H ₂₃ ClNO ₉ [M+H] ⁺ Calculated values: 456.1056, found: 456.1049.

example II-18 preparation of Compound II-18

2-bromo-4-methoxybenzonitrile (105.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 110.0mg as a clear oil with a yield of 44%. ¹ H NMR(600MHz,CDCl ₃ )δ7.78(d,J＝8.8Hz,1H),7.23(d,J＝2.5Hz,1H),6.91(dd,J＝8.8,2.5Hz,1H),6.11(d,J＝7.8Hz,1H),5.33(t,J＝4.2Hz,1H),4.98(m,1H),4.63–4.58(m,1H),4.32(dd,J＝12.1,5.2Hz,1H),4.21(dd,J＝12.1,2.7Hz,1H),3.87–3.83(m,4H),2.16(s,3H),2.10(s,3H),2.00(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.70,169.58,169.43,162.24,133.05,123.34,119.76,113.26,93.41,70.65,68.04,67.37,63.22,55.73,20.86,20.80,20.69.HRMS(ESI)：C ₂₀ H ₂₃ BrNO ₉ [M+H] ⁺ Calculated values: 500.0551, found: 500.0558.

example II-19 preparation of Compound II-19

2-bromo-5-methoxybenzonitrile (105.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 123.0mg as a clear oil with a yield of 50%. ¹ H NMR(500MHz,CDCl ₃ )δ7.57(d,J＝8.9Hz,1H),7.33(d,J＝3.1Hz,1H),6.93(dd,J＝8.9,3.1Hz,1H),6.14(d,J＝7.8Hz,1H),5.36(t,J＝4.2Hz,1H),5.00(m,1H),4.66(m,1H),4.34(dd,J＝12.2,5.2Hz,1H),4.23(dd,J＝12.2,2.8Hz,1H),3.88(m,1H),3.84(s,3H),2.16(s,3H),2.10(s,3H),2.02(s,3H). ¹³ C NMR(126MHz,CDCl ₃ )δ170.66,169.55,169.37,158.57,135.05,119.21,116.64,112.37,93.40,77.24,76.02,70.72,68.15,67.31,63.13,60.36,55.68,20.82,20.76,20.67.HRMS(ESI)：C ₂₀ H ₂₃ BrNO ₉ [M+H] ⁺ Calculated value:500.0551, found: 500.0556.

example II-20 preparation of Compound II-20

2-Bromopiperazine (112.5 mg,0.5 mmol) and beta-D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give 139.3mg of the product as a clear oil in 54% yield. ¹ H NMR(500MHz,CDCl ₃ )δ7.28(s,1H),7.13(s,1H),6.12(d,J＝7.8Hz,1H),6.07(s,2H),5.33(t,J＝4.2Hz,1H),4.99(m,J＝8.7,4.6,0.8Hz,1H),4.62(m,J＝7.8,3.7,0.9Hz,1H),4.33(dd,J＝12.2,5.2Hz,1H),4.22(dd,J＝12.2,2.8Hz,1H),3.84(m,J＝8.3,5.2,2.7Hz,1H),2.16(s,3H),2.10(s,3H),2.03(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.68,169.55,169.38,165.46,150.97,147.25,128.36,114.32,110.99,102.56,93.29,75.71,70.61,68.08,67.35,63.19,20.81,20.76,20.68.HRMS(ESI)：C ₂₀ H ₂₁ BrNO ₁₀ [M+H] ⁺ Calculated values: 514.0343, found: 514.0354.

example II-21 preparation of Compound II-21

Piperonyl cyanide (73.5 mg,0.5 mmol) and beta-D-galactose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 97.7mg as a clear oil with a yield of 45%. ¹ H NMR(500MHz,CDCl ₃ )δ7.50(dd,J＝8.1,1.7Hz,1H),7.37(d,J＝1.7Hz,1H),6.78(d,J＝8.1Hz,1H),6.03–5.93(m,3H),5.41(s,1H),4.98(dd,J＝7.2,3.1Hz,1H),4.61(t,J＝7.1Hz,1H),4.22(m,1H),4.13(m,2H),2.10(s,3H),2.06(s,3H),2.00(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ169.98,169.53,169.51,165.17,150.85,147.32,123.75,119.90,108.19,107.72,101.32,93.63,76.17,71.33,68.80,65.72,60.88,20.29,20.22,20.15.HRMS(ESI)：C ₂₀ H ₂₂ NO ₁₀ [M+H] ⁺ Calculated values: 436.1238, found: 436.1247.

example II-22 preparation of Compound II-22

Piperonyl cyanide (73.5 mg,0.5 mmol) and alpha-D-mannopyranoate (195 mg,0.5 mmol) were synthesized as described for II-1 to give 132.0mg total as a clear oil with 61% yield. ¹ H NMR(600MHz,CDCl ₃ )δ7.62(dd,J＝8.2,1.7Hz,1H),7.49(d,J＝1.6Hz,1H),6.86(d,J＝8.2Hz,1H),6.05(s,2H),5.74(d,J＝5.5Hz,1H),5.40(dd,J＝8.4,4.9Hz,1H),5.14(t,J＝8.2Hz,1H),4.81(t,J＝5.2Hz,1H),4.24(dd,J＝12.0,6.4Hz,1H),4.16(dd,J＝12.0,3.4Hz,1H),3.83(m,1H),2.12(s,3H),2.08(s,3H),2.04(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.30,169.76,168.95,167.85,151.03,147.36,124.17,119.55,108.52,107.79,101.35,93.19,76.32,72.86,68.52,66.09,63.27,20.29,20.27.HRMS(ESI)：C ₂₀ H ₂₂ NO ₁₀ [M+H] ⁺ Calculated values: 436.1238, found: 436.1238.

Example II-23 preparation of Compound II-23

2-bromo-3, 4, 5-trimethoxy-benzonitrile (135.5 mg,0.5 mmol) and α -D-mannose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give 63.9mg total product as a clear oil in 23% yield. ¹ H NMR(600MHz,CDCl ₃ )δ7.24(s,1H),6.40(d,J＝6.2Hz,1H),5.39(d,J＝1.2Hz,1H),5.01(d,J＝6.2Hz,1H),4.95(m,1H),4.46(dd,J＝12.3,2.6Hz,1H),4.31(t,J＝6.7Hz,1H),4.25(dd,J＝7.1,5.1Hz,1H),3.94(s,3H),3.92(s,3H),3.89(s,3H),2.15(s,3H),2.09(s,3H),2.05(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ171.87,171.56,170.92,167.13,154.11,153.03,147.40,132.31,124.44,111.73,104.31,87.02,83.62,79.64,70.71,64.19,62.59,62.47,57.81,22.26,22.16. HRMS(ESI)：C ₂₂ H ₂₇ BrNO ₁₁ [M+H] ⁺ Calculated values: 560.0762, found: 560.0764.

example II-24 preparation of Compound II-24

2-bromo-3, 4, 5-trimethoxy-benzonitrile (135.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for II-1 to give 121.4mg total as a clear oil with a yield of 44%. ¹ H NMR(500MHz,CDCl ₃ )δ7.17(s,1H),6.10(d,J＝7.7Hz,1H),5.37–5.35(m,1H),5.00(dd,J＝9.2,4.8Hz,1H),4.63(dd,J＝7.8,4.0Hz,1H),4.36–4.29(m,2H),4.23–4.19(m,1H),3.94(s,3H),3.90(s,6H),2.15(s,3H),2.10(s,3H),2.02(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.20,169.07,168.97,165.31,152.08,145.62,122.64,110.06,92.96,70.63,67.62,66.83,62.52,60.72,60.59,55.84,20.36,20.31,20.22.HRMS(ESI)：C ₂₂ H ₂₇ BrNO ₁₁ [M+H] ⁺ Calculated values: 560.0762, found: 560.0761.

example II-25 preparation of Compound II-25

Benzonitrile (51.5 mg,0.5 mmol) and 5-deoxy-1, 2, 3-triacetylribofuranose (130 mg,0.5 mmol) are synthesized as described for II-1 to give 129.5mg as a clear oil in 50% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.07–7.95(m,2H),7.52(m,1H),7.49–7.39(m,2H),6.18(d,J＝5.6Hz,1H),5.17(t,J＝5.6Hz,1H),4.49(dd,J＝9.3,5.6Hz,1H),3.80–3.69(m,1H),2.15(s,3H),1.32(d,J＝6.1Hz,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.34,167.25,132.35,128.85,128.52,128.44,126.21,100.00,78.46,78.23,71.61,20.54,16.60.HRMS(ESI)：C ₁₄ H ₁₆ NO ₄ [M+H] ⁺ Calculated values: 262.1074, found: 262.1075。

EXAMPLE II-26 preparation of Compound II-26

Benzonitrile (51.5 mg,0.5 mmol) and β -D-ribofuranosyl tetraacetate (159 mg,0.5 mmol) were synthesized as described for II-1 to give 129.5mg as a clear oil with a yield of 81%. ¹ H NMR(600MHz,CDCl ₃ )δ8.04(m,4H),7.57(m,2H),7.47(m,4H),6.33(d,J＝6.1Hz,1H),6.29(d,J＝5.6Hz,1H),5.34(m,1H),5.24(t,J＝5.7Hz,1H),5.06(dd,J＝6.2,1.0Hz,1H),4.87(dd,J＝9.3,5.9Hz,1H),4.43(dd,J＝12.4,2.7Hz,1H),4.33(m,1H),4.23(dd,J＝12.4,5.0Hz,1H),4.07(m,2H),3.92(m,1H),2.18(d,J＝5.8Hz,6H),2.11(s,3H),1.91(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.7,170.1,167.5,132.5,129.0,128.9,128.6,128.5,126.1,100.7,78.1,74.0,73.0,62.0,20.8,20.5.HRMS(ESI)：C ₁₄ H ₁₆ NO ₄ [M+H] ⁺ Calculated values: 320.1129, found: 320.1128.

example II-27 preparation of Compound II-27

Piperonyl cyanide (73.5 mg,0.5 mmol) and 5-deoxy-1, 2,3-Triacetylribofuranose (130 mg,0.5 mmol) was synthesized as described in II-1 to yield 77.5mg of the product as a clear oil in 51%. ¹ H NMR(500MHz,CDCl ₃ )δ7.7(ddd,J＝8.2,3.1,1.7Hz,1H),7.5(dd,J＝4.1,1.7Hz,1H),6.9(d,J＝8.2Hz,1H),6.1(s,2H),5.6–5.4(m,1H),5.4–5.3(m,1H),5.3–5.1(m,1H),4.5–4.3(m,1H),2.1(d,J＝46.9Hz,3H),1.4(dd,J＝35.9,6.4Hz,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.0,164.8,152.1,147.8,125.7,123.2,109.5,108.1,101.9,100.1,95.4,76.4,75.0,20.6,20.3.HRMS(ESI)：C ₁₅ H ₁₆ NO ₆ [M+H] ⁺ Calculated values: 306.0972, found: 306.0978.

example II-28 preparation of Compound II-28

2-Chlorobenzonitrile (68.5 mg,0.5 mmol) and beta-D-ribofuranosyl tetraacetate (159 mg,0.5 mmol) were synthesized as described for II-1 to give 126.0mg as a clear oil with a yield of 71%. ¹ H NMR(500MHz,CDCl ₃ )δ7.84(dd,J＝7.8,1.7Hz,1H),7.50(dd,J＝8.0,1.4Hz,1H),7.45(td,J＝8.1,7.7,1.7Hz,1H),7.35(td,J＝7.5,1.4Hz,1H),6.32(d,J＝5.7Hz,1H),5.26(t,J＝5.8Hz,1H),4.86(dd,J＝9.4,5.8Hz,1H),4.46(dd,J＝12.3,2.7Hz,1H),4.26(dd,J＝12.3,5.1Hz,1H),4.02(m,1H),2.16(s,3H),2.12(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.67,170.09,133.71,132.50,131.73,130.91,126.66,100.61,78.20,74.00,73.01,61.93,20.76,20.52.HRMS(ESI)：C ₁₆ H ₁₇ ClNO ₆ [M+H] ⁺ Calculated values: 354.0739, found: 354.0742.

example II-29 preparation of Compound II-29

2-bromoxynil (90.5 mg,0.5 mmol) and β -D-ribofuranosyl tetraacetate (159 mg,0.5 mmol) were synthesized as described for II-1 to give 156.0mg as a clear oil with a yield of 79%. ¹ H NMR(500MHz,CDCl ₃ )δ7.79–7.73(m,1H),7.68(dd,J＝7.7,1.5Hz,1H),7.37(m,2H),6.30(d,J＝5.7Hz,1H),5.25(t,J＝5.8Hz,1H),4.86(dd,J＝9.5,5.8Hz,1H),4.45(dd,J＝12.4,2.7Hz,1H),4.25(dd,J＝12.4,5.0Hz,1H),4.06(m,1H),2.15(s,3H),2.11(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.65,170.07,167.24,134.10,132.49,131.78,128.44,127.20,121.78,100.57,78.37,74.00,73.03,61.93,20.76,20.57.HRMS(ESI)：C ₁₆ H ₁₇ BrNO ₆ [M+H] ⁺ Calculated values: 398.0234, found: 398.0229.

example II-30 preparation of Compound II-30

2-iodobenzonitrile (114.5 mg,0.5 mmol) and β -D-ribofuranosyl tetraacetate (159 mg,0.5 mmol) were synthesized as described for II-1 to give 142.6mg as a clear oil with a yield of 64%. ¹ H NMR(500MHz,CDCl ₃ )δ7.99(dd,J＝7.9,1.1Hz,1H),7.71(dd,J＝7.8,1.7Hz,1H),7.42(td,J＝7.6,1.2Hz,1H),7.17(td,J＝7.7,1.7Hz,1H),6.30(d,J＝5.7Hz,1H),5.25(t,J＝5.7Hz,1H),4.88(dd,J＝9.5,5.7Hz,1H),4.45(dd,J＝12.3,2.7Hz,1H),4.25(dd,J＝12.4,5.0Hz,1H),4.17–4.08(m,1H),2.15(s,3H),2.11(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.64,170.05,167.93,140.95,132.43,131.32,127.88,100.57,94.27,78.44,74.06,73.07,61.96,20.77,20.68.HRMS(ESI)：C ₁₆ H ₁₇ INO ₆ [M+H] ⁺ Calculated values: 446.0095, found: 446.0094.

example II-31 preparation of Compound II-31

Piperonyl cyanide (73.5 mg,0.5 mmol) and D- (+) -cellobiose octaacetate (399 mg,0.5 mmol) were synthesized as described for II-1 to give a total of 151.1mg as a clear oil with a yield of 42%. ¹ H NMR(600MHz,CDCl ₃ )δ7.61(dd,J＝8.2,1.7Hz,1H),7.48(d,J＝1.7Hz,1H),6.88(d,J＝8.1Hz,1H),6.05(s,2H),5.97(d,J＝7.4Hz,1H),5.63(s,1H),5.19–5.08(m,2H),4.89(dd,J＝9.3,8.0Hz,1H),4.66(d,J＝8.1Hz,1H),4.54(ddd,J＝7.4,3.3,1.1Hz,1H),4.26(dd,J＝12.3,4.4Hz,1H),4.22(dd,J＝12.0,2.5Hz,1H),4.17(dd,J＝12.3,2.6Hz,1H),4.15–4.11(m,1H),3.76–3.66(m,2H),3.46(ddd,J＝9.0,5.1,2.5Hz,1H),2.15(s,3H),2.12(s,3H),2.11(s,3H),2.02(s,3H),1.97(s,3H),1.97(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.54,170.10,169.28,169.26,169.11,166.80,151.33,147.73,124.45,119.66,108.86,108.22,101.67,101.54,92.45,75.35,72.84,71.84,71.21,69.76,67.99,67.21,63.48,61.64,20.82,20.77,20.62,20.48,20.45,20.34.HRMS(ESI)：C ₃₂ H ₃₈ NO ₁₈ [M+H] ⁺ Calculated values: 724.2083, found: 724.2100.

example II-32 preparation of Compound II-32

Piperonyl cyanide (73.5 mg,0.5 mmol) and maltotriose undecanoate (483 mg,0.5 mmol) were synthesized as described for II-1 to give 91.1mg total product as a white powder in 18% yield. ¹ H NMR(500MHz,CDCl ₃ )δ7.68(dd,J＝8.1,1.7Hz,1H),7.55(d,J＝1.7Hz,1H),6.97(d,J＝8.2Hz,1H),6.05(d,J＝1.5Hz,2H),5.39(d,J＝4.0Hz,1H),5.36–5.29(m,3H),5.24(dd,J＝3.4,1.6Hz,1H),5.07(d,J＝9.9Hz,1H),4.85(ddd,J＝15.8,10.3,4.0Hz,2H),4.59–4.54(m,1H),4.43(dd,J＝12.4,1.8Hz,1H),4.31–4.21(m,4H),4.18–4.13(m,1H),4.07–4.03(m,1H),3.93(dd,J＝7.1,2.5Hz,3H),3.72(dt,J＝8.6,1.7Hz,1H),3.61(td,J＝5.3,2.6Hz,1H),2.16(s,6H),2.14(s,6H),2.11(s,3H),2.04(s,6H),2.01(s,3H),2.00(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.67,170.50,170.48,170.40,170.21,169.83,169.63,169.51,169.42,167.24,151.37,147.89,124.62,119.85,108.99,108.63,101.66,95.77,95.55,92.32,74.82,73.86,72.85,72.05,70.68,70.04,69.42,68.88,68.58,68.52,67.88,67.39,64.01,62.55,61.41,20.90,20.69,20.66,20.57.HRMS(ESI)：C ₄₄ H ₅₃ NNaO ₂₆ [M+Na] ⁺ Calculated values: 1034.2748, found: 1034.2722.

the following are examples of the preparation of compounds of formula III

Example III-1 preparation of Compound III-1

The method comprises the following steps: beta-D-glucose pentaacetate (195 mg,0.5 mmol) was dissolved in a dry round bottom flask with 10ml of ultra-dry dichloromethane and benzonitrile (50. Mu.l, 0.5 mmol) and trifluoromethanesulfonic acid (135. Mu.l, 1.5 mmol) was added and reacted for 2 hours. After the completion of the reaction, deionized water (20 ml) was added to quench the reaction, and the reaction mixture was extracted twice with ethyl acetate (20 ml). The organic phases were then combined and washed once with deionized water (30 ml), once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate and filtered. After spin-drying using a rotary evaporator, the mixture was redissolved in dichloromethane, stirred in silica gel, and separated by silica gel column chromatography PE: ea=3:1 to give a yellowish oily product (white solid precipitated by refrigeration and standing) in a total of 98.5mg, with a yield of 60%. ¹ H NMR(600MHz,CDCl ₃ )δ8.13–8.06(m,2H),7.61–7.52(m,1H),7.51–7.42(m,2H),6.63(dd,J＝10.4,2.6Hz,1H),6.29(dd,J＝10.4,1.8Hz,1H),5.77(d,J＝1.0Hz,1H),4.59–4.50(m,1H),4.27–4.17(m,2H),2.08(s,3H),2.06(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.83,168.74,167.19,134.83,132.82,129.19,128.48,126.20,122.07,101.40,96.82,69.72,65.17,21.66,20.81.HRMS(ESI):C ₁₇ H ₁₈ NO ₆ [M+H] ⁺ Calculated 332.1129, found 332.1123.

The second method is as follows: benzonitrile (51.5 mg,0.5 mmol)And β -D-galactose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 129.7mg of the product as a yellow oil in 79% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.09–8.02(m,2H),7.55–7.48(m,1H),7.45–7.38(m,2H),6.60(dd,J＝10.4,2.6Hz,1H),6.26(dd,J＝10.4,1.9Hz,1H),5.73(d,J＝0.8Hz,1H),4.54–4.47(m,1H),4.24–4.14(m,2H),2.04(s,3H),2.03(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.35,168.27,166.70,134.38,132.37,128.70,128.02,125.71,121.57,100.92,96.33,69.24,64.70,21.20,20.34.HRMS(ESI):C ₁₇ H ₁₈ NO ₆ [M+H] ⁺ Calculated 332.1129, found 332.1138.

And a third method: benzonitrile (51.5 mg,0.5 mmol) and α -D-pentaacetylmannose (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 62.4mg total as yellow oil in 38% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.10(dd,J＝8.2,1.4Hz,2H),7.61–7.53(m,1H),7.46(t,J＝7.6Hz,2H),6.64(dd,J＝10.4,2.6Hz,1H),6.31(dd,J＝10.4,1.8Hz,1H),5.78(d,J＝1.0Hz,1H),4.55(m,J＝6.8, 4.7,2.1Hz,1H),4.29–4.18(m,2H),2.09(s,3H),2.07(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.83,168.74,167.20,134.84,132.83,129.19,128.49,126.20,122.06,101.40,96.81,69.71,65.17,21.66,20.81.HRMS(ESI):C ₁₇ H ₁₈ NO ₆ [M+H] ⁺ Calculated 332.1129, found 332.1123.

Example III-2 preparation of Compound III-2

2-Methylbenzonitrile (58.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give a total of 83.1mg as a clear oil in 48% yield. ¹ H NMR(400MHz,CDCl ₃ )δ8.01–7.96(m,1H),7.42(m,1H),7.30(d,J＝3.0Hz,1H),7.26(d,J＝7.8Hz,1H),6.64(dd,J＝10.4,2.6Hz,1H),6.30(dd,J＝10.4,1.9Hz,1H),5.79(d,J＝0.8Hz,1H),4.54(d,J＝5.9Hz,1H),4.30–4.19(m,2H),2.70(s,3H),2.10(s,3H),2.09(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.83,168.81,167.41,140.41,134.70,131.96,131.57,130.77,125.71,125.22,122.14,100.49,97.13,69.73,65.20,22.23,21.69,20.83.HRMS(ESI):C ₁₈ H ₂₀ NO ₆ [M+H] ⁺ Calculated 346.1285, found 346.1292.

Example III-3 preparation of Compound III-3

4-Methoxybenzonitrile (66.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 117.3mg of the product as a yellow oil in 65% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.01(d,J＝8.9Hz,2H),6.92(d,J＝9.0Hz,2H),6.60(dd,J＝10.4,2.6Hz,1H),6.26(dd,J＝10.4,1.8Hz,1H),5.71(d,J＝0.9Hz,1H),4.50(m,1H),4.23(s,2H),3.84(s,3H),2.05(s,3H),2.03(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.39,168.35,166.67,162.85,134.36,130.68,121.67,117.98,113.42,100.91,96.32,69.21,64.72,54.99,21.23,20.37.HRMS(ESI):C ₁₈ H ₂₀ NO ₇ [M+H] ⁺ Calculated 362.1234, found 362.1232.

Example III-4 preparation of Compound III-4

3-Methoxybenzonitrile (66.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 88.1mg of the product as a yellow oil in 49% yield. ¹ H NMR(500MHz,CDCl3)δ7.70–7.62(m,2H),7.37(t,J＝8.0Hz,1H),7.12(dd,J＝8.3,2.1Hz,1H),6.63(dd,J＝10.4,2.6Hz,1H),6.31(dd,J＝10.4,1.8Hz,1H),5.78(s,1H),4.59–4.52(m,1H),4.24(qd,J＝11.7,5.5Hz,2H),3.87(s,3H),2.09(d,J＝9.3Hz,6H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.85,168.74,167.20,159.57,134.86,129.57,127.39,122.06,121.68,119.91,113.16,101.47,96.74,69.73,65.17,55.50,21.66,20.81.HRMS(ESI):C ₁₈ H ₂₀ NO ₇ [M+H] ⁺ Calculated 362.1234, found 362.1226.

Example III-5 preparation of Compound III-5

3,4, 5-trimethoxybenzonitrile (96.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 192.0mg of the product as a yellow oil in 91% yield. ¹ H NMR(500MHz,CDCl ₃ )δ7.33(s,2H),6.60(dd,J＝10.4,2.6Hz,1H),6.30(dd,J＝10.4,1.8Hz,1H),5.75(d,J＝0.5Hz,1H),4.54(ddd,J＝6.3,3.7,2.4Hz,1H),4.22(qd,J＝11.7,5.5Hz,2H),3.90(d,J＝4.7Hz,9H),2.07(d,J＝6.7Hz,6H).13C NMR(125MHz,CDCl ₃ )δ170.80,168.71,167.07,153.09,142.14,134.95,121.99,121.13,106.38,101.60,96.65,69.71,65.14,60.95,56.31,21.65,20.79.HRMS(ESI):C ₂₀ H ₂₄ NO ₉ [M+H] ⁺ Calculated 422.1455, found 422.1446.

Example III-6 preparation of Compound III-6

4-fluorobenzonitrile (60.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give a total of 41.7mg as a yellow oil in 24% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.12–8.04(m,2H),7.12(dd,J＝9.6,7.6Hz,2H),6.60(dd,J＝10.4,2.6Hz,1H), 6.29(dd,J＝10.4,1.9Hz,1H),5.74(d,J＝0.9Hz,1H),4.52(m,1H),4.25–4.16(m,2H),2.06(s,3H),2.05(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.74,168.66,166.19,134.91,131.65,131.58,121.95,115.83,115.66,101.48,96.82,69.70,65.11,21.61,20.76.HRMS(ESI):C ₁₇ H ₁₇ FNO ₆ [M+H] ⁺ Calculated 350.1034, found 350.1043.

Example III-7 preparation of Compound III-7

4-Chlorobenzonitrile (68.5 mg,0.5 mmol) and beta-D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 54.2mg total as yellow oil with a yield of 30%. ¹ H NMR(500MHz,CDCl ₃ )δ8.03(d,J＝8.6Hz,2H),7.44(d,J＝8.6Hz,2H),6.62(dd,J＝10.4,2.6Hz,1H),6.31(dd,J＝10.4,1.8Hz,1H),5.76(d,J＝0.8Hz,1H),4.58–4.50(m,1H),4.28–4.18(m,2H),2.09(s,3H),2.07(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.78,168.67,166.29,139.22,134.93,130.50,128.86,124.71,121.95,101.50,96.83,69.74,65.11,21.64,20.80.HRMS(ESI):C ₁₇ H ₁₇ ClNO ₆ [M+H] ⁺ Calculated 366.0739, found 366.0741.

Example III-8 preparation of Compound III-8

4-bromoxynil (91.0 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 107.4mg of the product as a yellow oil in 53% yield. ¹ H NMR(500MHz,CDCl ₃ )δ7.95(d,J＝8.6Hz,2H),7.60(d,J＝8.6Hz,2H),6.62(dd,J＝10.4,2.6Hz,1H),6.30(dd,J＝10.4,1.9Hz,1H),5.76(d,J＝0.9Hz,1H),4.54(ddt,J＝6.8,4.5,2.0Hz,1H),4.27–4.18(m,2H),2.08(s,3H),2.07(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.78,168.66,166.40,134.94,131.84,130.62,127.82,125.16,121.94,101.50,96.83,69.74,65.11,21.64,20.80.HRMS(ESI):C ₁₇ H ₁₇ BrNO ₆ [M+H] ⁺ Calculated 410.0234, found 410.0237.

Example III-9 preparation of Compound III-9

4-Trifluoromethylbenzonitrile (85.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 68.4mg of the product as a yellow oil in 34% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.20(d,J＝8.2Hz,2H),7.72(d,J＝8.3Hz,2H),6.63(dd,J＝10.4,2.6Hz,1H),6.32(dd,J＝10.4,1.8Hz,1H),5.79(s,1H),4.59–4.51(m,1H),4.29–4.17(m,2H),2.08(d,J＝3.6Hz,6H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.28,168.13,165.35,134.51,129.06,124.97,121.35,101.05,96.29,69.28,64.58,21.09,20.26.HRMS(ESI):C ₁₈ H ₁₇ F ₃ NO ₆ [M+H] ⁺ Calculated 400.1002, found 400.1006.

Example III-10 preparation of Compound III-10

Synthesis of 4-ethynylbenzonitrile (63.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) as described for Compound III-1 gave a total of 37.6mg as a yellow oil in 32% 1H NMR (500 MHz, CDCl) ₃ )δ8.08–8.02(m,2H),7.61–7.54(m,2H),6.63(dd,J＝10.4,2.6Hz,1H),6.30(dd,J＝10.4,1.8Hz,1H),5.78(s,J＝0.6Hz,1H),4.55(ddd,J＝5.5,3.7,2.4Hz,1H),4.29–4.17(m,2H),3.26(s,1H),2.08(d,J＝7.3Hz,6H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.83,168.71,166.51,134.92,132.16,129.05,126.66,126.30,121.98,101.47,96.81,82.78,80.24,69.75,65.13,21.65,20.80.HRMS(ESI)：C ₁₉ H ₁₈ NO ₆ [M+H] ⁺ Calculated values: 356.1129, found: 356.1131.

example III-11 preparation of Compound III-11

2-chloro-4-methoxybenzonitrile (83.7 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 28.05mg of the product as a yellow oil in 14% yield. ¹ H NMR(500MHz,CDCl ₃ )δ7.95(d,J＝8.8Hz,1H),7.01(d,J＝2.5Hz,1H),6.85(dd,J＝8.8,2.5Hz,1H),6.64(dd,J＝10.4,2.6Hz,1H),6.29(dd,J＝10.4,1.8Hz,1H),5.77(s,1H),4.53(td,J＝4.6,2.4Hz,1H),4.24(qd,J＝11.7,5.6Hz,2H),3.86(s,3H),2.09(d,J＝7.5Hz,6H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.83,168.79,165.43,162.66,135.98,134.78,133.65,122.02,117.45,116.51,112.72,100.70,96.90,69.75,65.16,55.73,21.67,20.82.HRMS(ESI):C ₁₈ H ₁₉ ClNO ₇ [M+H] ⁺ Calculated 396.0845, found 396.0840.

Example III-12 preparation of Compound III-12

2-bromo-4-methoxybenzonitrile (106.0 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 86.7mg total as yellow oil with 40% yield. ¹ H NMR(500MHz,CDCl ₃ )δ7.92(d,J＝8.8Hz,1H),7.23(d,J＝2.5Hz,1H),6.91(dd,J＝8.8,2.5Hz,1H),6.67(dd,J＝10.4,2.6Hz,1H),6.30(dd,J＝10.4,1.9Hz,1H),5.77(s,1H),4.53(td,J＝4.7,2.6Hz,1H),4.25(qd,J＝11.6,5.6Hz,2H),3.87(s,3H),2.10(d,J＝6.4Hz,6H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.33,168.30,165.45,161.91,134.24,133.26,123.15,121.55,119.40,118.99,112.66,100.37,96.41,69.24,64.68,55.22,21.19,20.33.HRMS(ESI):C ₁₈ H ₁₉ BrNO ₇ [M+H] ⁺ Calculated 440.0339, found 440.0337.

Example III-13 preparation of Compound III-13

Synthesis of 4-cyanobiphenyl (90.0 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) as described for Compound III-1 gave a yellow oily product, total 69.01mg, 34% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.19–8.11(m,2H),7.72–7.59(m,4H),7.47(dd,J＝10.4,4.7Hz,2H),7.43–7.36(m,1H),6.64(dd,J＝10.4,2.6Hz,1H),6.30(dd,J＝10.4,1.8Hz,1H),5.78(d,J＝0.4Hz,1H),4.54(td,J＝4.6,2.7Hz,1H),4.23(qd,J＝11.7,5.6Hz,2H),2.07(d,J＝7.0Hz,6H).

¹³ C NMR(125MHz,CDCl ₃ )δ170.85,168.78,167.09,145.58,139.91,134.87,129.71,128.95,128.21,127.19,124.98,122.11,101.45,96.88,69.75,65.20,21.69,20.83.HRMS(ESI):C ₂₃ H ₂₃ NO ₆ [M+H] ⁺ Calculated 408.1442, found 408.1453.

Example III-14 preparation of Compound III-14

2-Naphthol (76.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 141.0mg of the product as a yellow oil in 74% yield. ¹ H NMR(500MHz, CDCl ₃ )δ8.59(t,J＝1.1Hz,1H),8.15(dd,J＝8.6,1.7Hz,1H),7.95–7.86(m,3H),7.60–7.53(m,2H),6.69(dd,J＝10.4,2.6Hz,1H),6.32(dd,J＝10.4,1.8Hz,1H),5.83(d,J＝0.9Hz,1H),4.57(m,1H),4.29–4.19(m,2H),2.08(s,6H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.80,168.80,167.31,135.39,134.93,132.46,130.40,129.15,128.34,128.26,127.83,126.80,124.93,123.45,122.09,101.50,96.89,69.77,65.17,21.69,20.81.HRMS(ESI):C ₂₁ H ₂₀ NO ₆ [M+H] ⁺ Calculated 382.1285, found 382.1289.

Example III-15 preparation of Compound III-15

2-Cyanofuran (46.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give a total of 87.0mg as a yellow oil in 54% yield. ¹ H NMR(600MHz,CDCl ₃ )δ7.64(d,J＝0.9Hz,1H),7.23(d,J＝3.5Hz,1H),6.63–6.50(m,2H),6.30(dd,J＝10.4,1.8Hz,1H),5.77(s,1H),4.54(td,J＝4.4,2.6Hz,1H),4.22(ddd,J＝16.1,11.7,5.6Hz,3H),2.08(d,J＝6.4Hz,6H). ¹³ C NMR(150MHz,CDCl ₃ )δ170.76,170.42,168.26,158.63,146.30,141.02,134.54,121.25,117.32,111.62,100.90,95.95,69.26,64.63,21.19,20.34.HRMS(ESI):C ₁₅ H ₁₆ NO ₇ [M+H] ⁺ Calculated 322.0921, found 322.0925.

Example III-16 preparation of Compound III-16

3-Cyanothiophene (46.5 mg,0.5 mmol) and β -D-glucose pentaacetate (195 mg,0.5 mmol) were synthesized as described for compound III-1 to give 112.07mg as a yellow oily product in 67% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.13(dd,J＝3.0,1.1Hz,1H),7.65(dd,J＝5.1,1.1Hz,1H),7.38(dd,J＝5.1,3.0Hz,1H),6.61(dd,J＝10.4,2.6Hz,1H),6.30(dd,J＝10.4,1.8Hz,1H),5.75(s,1H),4.54(td,J＝4.6,2.7Hz,1H),4.23(qd,J＝11.7,5.6Hz,2H),2.08(d,J＝9.2Hz,6H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.84,168.75,163.31,134.86,131.68,128.56,127.60(s,3H),126.58,122.02,101.33,96.80,69.73,65.16,21.66,20.81.HRMS(ESI):C ₁₅ H ₁₅ NO ₆ S[M+H] ⁺ Calculated 338.0693, found 338.0694.

Example III-17 preparation of Compound III-17

Benzonitrile (51.5 mg,0.5 mmol) and 1,2,3, 4-tetra-O-acetyl-Alpha-L-fucose (165 mg,0.5 mmol) were synthesized as described for compound III-1 to give a total of 9.5mg as yellow oil in 7% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.11(dd,J＝8.4,1.3Hz,2H),7.60–7.53(m,1H),7.50–7.42(m,2H),6.57(dd,J＝10.3,2.5Hz,1H),6.26(dd,J＝10.3,1.6Hz,1H),5.71(d,J＝0.7Hz,1H),4.48–4.37(m,1H),2.06(s,3H),1.38(d,J＝6.9Hz,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ168.81,167.16,140.20,132.68,129.18,128.43,126.42,119.96,101.50,96.90,67.63,21.71,20.63.HRMS(ESI):C ₁₅ H ₁₆ NO ₄ [M+H] ⁺ Calculated 274.1074, found 274.1075.

Example III-18 preparation of Compound III-18

Piperonyl cyanide (73.5 mg,0.5 mmol) and 1,2,3, 4-tetra-O-acetyl-Alpha-L-fucopyranoside (165 mg,0.5 mmol) were synthesized as described for compound III-1 to give 45.6mg total as yellow oil in 29% yield. ¹ H NMR(500MHz,CDCl ₃ )δ7.66(dd,J＝8.2,1.7Hz,1H),7.54(d,J＝1.7Hz,1H),6.85(d,J＝8.1Hz,1H),6.54(dd,J＝10.3,2.5Hz,1H),6.23(dd,J＝10.3,1.6Hz,1H),6.04(s,2H),5.69–5.61(m,1H),4.44–4.33(m,1H),2.05(s,3H),1.36(d,J＝6.9Hz,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ168.79,166.74,151.44,147.76,140.16,124.74,120.21,119.94,109.03,108.16,101.75,101.52,96.83,67.58,21.71,20.61.HRMS(ESI)：C ₁₆ H ₁₆ NO ₆ [M+H] ⁺ Calculated values: 318.0972, found: 318.0973.

example III-19 preparation of Compound III-19

The method comprises the following steps: benzonitrile (51.5 mg,0.5 mmol) and 1,2,3, 4-tetra-O-acetyl-. Beta. -D-ribopyranosyl-acetate (159 mg,0.5 mmol) were synthesized as described for compound III-1 to give a total of 43.4mg as a clear oily product (a: b=1:1) in 34% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.10–8.04(m,2H),7.56(dd,J＝10.6,4.3Hz, 1H),7.46(t,J＝7.7Hz,2H),6.50(dt,J＝10.5,1.8Hz,1H),6.39(dt,J＝10.5,3.3Hz,1H),5.87(s,1H),4.35–4.20(m,2H),2.11(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ168.71,166.64,134.82,132.64,128.98,128.47,126.45,120.78,101.41,97.36,60.89,21.70.HRMS(ESI):C ₁₄ H ₁₄ NO ₄ [M+H] ⁺ Calculated 260.0917, found 260.0914.

The second method is as follows: benzonitrile (51.5 mg,0.5 mmol) and 1,2,3, 4-tetra-O-acetyl- β -D-xylopyranose (159 mg,0.5 mmol) were synthesized as described for compound III-1 to give 49.6mg total of the product (a: b=1:1) as a clear oil with a yield of 38%. ¹ H NMR(500MHz,CDCl ₃ )δ8.08–8.01(m,2H),7.58–7.50(m,1H),7.43(dd,J＝10.7,4.7Hz,2H),6.48(dt,J＝10.5,1.9Hz,1H),6.36(dt,J＝10.5,3.3Hz,1H),5.85(s,1H),4.31–4.18(m,2H),2.08(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ168.27,166.19,134.38,132.19,128.53,128.01,125.98,120.31,100.94,96.89,60.44,21.26.HRMS(ESI):C ₁₄ H ₁₄ NO ₄ [M+H] ⁺ Calculated 260.0917, found 260.0916.

Example III-20 preparation of Compound III-20

The method comprises the following steps: piperonyl nitrile (73.5 mg,0.5 mmol) and 1,2,3, 4-tetra-O-acetyl-. Beta. -D-ribopyranose- (159 mg,0.5 mmol) were synthesized as described for compound III-1 to give 49.8mg total of the product (a: b=1:1) as a clear oil in 33% yield. ¹ H NMR(600MHz,CDCl ₃ )δ7.59(dd,J＝8.2,1.7Hz,1H),7.47(d,J＝1.7Hz,1H),6.82(d,J＝8.1Hz,1H),6.48-6.42(m,1H),6.38-6.32(m,1H),6.02(s,2H),5.78(s,1H),4.26–4.19(m,2H),2.06(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ168.30,165.81,150.94,147.31,134.42,124.07,120.19,119.70,108.37,107.73,101.32,100.92,96.72,60.50,21.29.HRMS(ESI)：C ₁₅ H ₁₄ NO ₆ [M+H] ⁺ Calculated values: 304.0816, found: 304.0820。

The second method is as follows: piperonyl cyanide (73.5 mg,0.5 mmol) and 1,2,3, 4-tetra-O-acetyl-beta-D-xylopyranose (159 mg,0.5 mmol) were synthesized as described for compound III-1 to give a total of 84.2mg of the product (a: b=1:1) as a clear oil in 56% yield. ¹ H NMR(600MHz,CDCl ₃ )δ7.59(dd,J＝8.2,1.7Hz,1H),7.47(d,J＝1.7Hz,1H),6.82(d,J＝8.2Hz,1H),6.47–6.42(m,1H),6.38–6.31(m,1H),6.01(s,2H),5.77(s,1H),4.26–4.18(m,2H),2.06(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ168.26,165.78,150.93,147.31,134.38,124.05,120.21,119.72,108.37,107.71,101.31,100.93,96.73,60.45,21.25.HRMS(ESI)：C ₁₅ H ₁₄ NO ₆ [M+H] ⁺ Calculated values: 304.0816, found: 304.0815..

Example III-21 preparation of Compound III-21

III-1 (33.1 mg of 0.2 mmol) was dissolved in a round bottom flask containing 3ml of thionyl chloride, heated at 60℃and nitrogen blanket for 2 hours, quenched by the addition of deionized water (20 ml) after the reaction was completed, and the reaction solution was extracted twice with ethyl acetate (20 ml). The organic phases were then combined and washed once with deionized water (30 ml), once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate and filtered, the organic phases were dried by spin-drying on a rotary evaporator and dissolved in dichloromethane, and the silica gel was column chromatographed (PE: ea=10:1). 15.3mg of the product was obtained as a yellow oil in 53% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.14–8.07(m,2H),7.60(t,J＝7.5Hz,1H),7.49(t,J＝7.8Hz,2H),7.29(s,1H),6.49(dd,J＝10.1,2.5Hz,1H),6.15(dd,J＝10.1,1.6Hz,1H),5.86(s,1H),4.51(t,J＝5.4Hz,1H),4.27–4.19(m,2H),2.10(s,3H). ¹³ C NMR(125MHz,CDCl3)δ170.79,167.16,133.09,131.36,129.26,128.57,125.94,125.23,100.47,96.56,69.83,64.93,53.42,20.79.HRMS(ESI):C ₁₅ H ₁₆ NO ₅ [M+H] ⁺ Calculated 290.1023, found 290.1018.

Example III-22 preparation of Compound III-22

1,2,3,4, 6-penta-O-pivaloyl-D-mannopyranose (300 mg,0.5 mmol) was dissolved in a dry round bottom flask containing 10ml of ultra-dry dichloromethane, after which trifluoromethanesulfonic acid (135. Mu.l, 1.5 mmol) was added and heated to 40℃and after 30 minutes of reaction benzonitrile (50. Mu.l, 0.5 mmol) was added and the reaction was continued under nitrogen for 1.5 hours. After the completion of the reaction, deionized water (20 ml) was added to quench the reaction, and the reaction mixture was extracted twice with ethyl acetate (20 ml). The organic phases were then combined and washed once with deionized water (30 ml), once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate and filtered. After spin-drying using a rotary evaporator, the mixture was redissolved in dichloromethane, stirred in silica gel, and separated by silica gel column chromatography PE: ea=3:1 to give 108.2mg of the product as a brown-yellow oil in 52% yield. ¹ H NMR(500MHz,CDCl3)δ8.10–8.04(m,2H),7.58–7.53(m,1H),7.44(dd,J＝8.4,7.1Hz,2H),6.58(dd,J＝10.4,2.5Hz,1H),6.29(dd,J＝10.4,1.7Hz,1H),4.53(dqt,J＝7.0,2.8,2.0Hz,1H),4.27(dd,J＝11.5,6.0Hz,1H),4.16(dd,J＝11.5,5.3Hz,1H),1.19(s,9H),1.15(s,9H). ¹³ C NMR(125MHz,CDCl3)δ178.22,176.46,167.30,135.11,132.77,129.14,128.49,126.27,121.83,101.46,96.61,69.81,64.90,39.37,38.82,27.12,26.81.LRMS(ESI):C ₂₃ H ₂₉ NO ₆ [M+H]+found 416.4.

The application examples of the oxazoline sugar as the synthesis intermediate in the formula I are as follows:

the following are examples of the preparation of compounds of formula IV:

example IV-1 preparation of Compound IV-1

Compound II-1 39mg,0.1 mmol) was dissolved in acetone (5 ml), followed by addition of 2M ethereal hydrochloride (100. Mu.l, 0.2 mmol), after stirring well, a drop of deionized water was added and after stirring at room temperature for two days a large amount of precipitate was precipitated. The white solid product, namely the hydrochloride of IV-1, is obtained by suction filtration, and the total yield is 27.5mg and 67 percent. ¹ H NMR(400MHz,CDCl ₃ )δ8.03(dd,J＝8.3,1.4Hz,2H),7.65–7.56(m,1H),7.47(t,J＝7.7Hz,2H),5.48(t,J＝9.7Hz,1H),5.13(m,2H),4.36(d,J＝8.7Hz,1H),4.29(dd,J＝12.3,4.9Hz,1H),4.17(dd,J＝12.3,2.3Hz,1H),3.85–3.75(m,1H),2.14(d,J＝1.0Hz,3H),2.07(d,J＝0.9Hz,3H),1.95(d,J＝0.9Hz,3H).HRMS(ESI)：C ₁₉ H ₂₄ NO ₉ [M+H] ⁺ Calculated values: 410.1446, found: 410.1441.

example IV-2 preparation of Compound IV-2

II-1 (3 g,7.67 mmol) was placed in a 100ml round bottom flask, 50ml of methanol was added to dissolve, triethylamine (5.3 ml,5 eq) was added to stir for 2 days, after completion of the reaction, the reaction mixture was spun dry, 2.2g of oily product was dissolved in 30ml of dry DMF, benzyl bromide (4.87 ml,5 eq) and 60% NaH (1.60 g,5 eq) were then added in sequence, reacted for 30 minutes under nitrogen protection, after completion of the TLC reaction, the reaction mixture was quenched with deionized water (50 ml), extracted twice with ethyl acetate (50 ml), combined with organic phase and washed twice (50 ml) with water, once with saturated sodium chloride (50 ml), dried over anhydrous sodium sulfate, and subtractedThe organic phase was evaporated to dryness under pressure, redissolved in dichloromethane and stirred using silica gel, and the yellow solid product was obtained after flash column chromatography elution, with a total of 2.53g, yield 62%. ¹ H NMR(600MHz,CDCl ₃ )δ7.97–7.95(m,1H),7.51(t,J＝7.4Hz,1H),7.41(d,J＝1.5Hz,2H),7.38–7.34(m,5H),7.33–7.29(m,5H),7.29–7.24(m,5H),7.18–7.16(m,1H),6.09(d,J＝7.6Hz,1H),4.85(d,J＝11.8Hz,1H),4.77–4.69(m,3H),4.67(dd,J＝7.5,4.6Hz,1H),4.60(d,J＝12.0Hz,1H),4.50(dd, J＝11.7,7.1Hz,2H),3.89(dd,J＝6.9,4.7Hz,1H),3.82(dd,J＝8.9,6.9Hz,1H),3.72(d,J＝2.9Hz,1H),3.63(d,J＝9.0Hz,1H). ¹³ C NMR(150MHz,CDCl ₃ )δ165.9,138.1,137.9,132.3,128.7,128.5,128.4,128.4,128.3,128.0,127.9,127.9,127.9,127.7,127.6,126.9,94.1,81.2,80.2,74.6,73.8,73.5,72.7,71.8,69.4.HRMS(ESI)：C ₃₄ H ₃₄ NO ₅ [M+H] ⁺ Calculated values: 536.2431, found: 536.2438.

the above compound (1 g,1.86 mmol) was placed in a 100ml round bottom flask, dissolved in 30ml acetone, then added with 2M diethyl ether hydrochloride solution (1 ml), followed by 10 drops of purified water, stirred at room temperature for 1 day, and then largely precipitated, and suction filtered to obtain a white solid product, namely hydrochloride IV-2, with a total of 0.857g and a yield of 83%. ¹ H NMR(500MHz,DMSO-d ₆ )δ9.06(s,2H),8.01–7.95(m,2H),7.71–7.65(m,1H),7.54(t,J＝7.8Hz,2H),7.35(d,J＝4.3Hz,4H),7.33–7.25(m,4H),7.20(dd,J＝7.6,1.9Hz,2H),7.17–7.06(m,3H),7.04–6.95(m,2H),5.13(t,J＝9.2Hz,1H),4.94(d,J＝9.0Hz,1H),4.71(dd,J＝11.0,6.9Hz,2H),4.61–4.48(m,4H),4.04(t,J＝9.2Hz,1H),3.90(m,1H),3.75–3.61(m,3H). ¹³ C NMR(125MHz,DMSO-d ₆ )δ206.94,165.33,138.24,138.18,137.96,134.04,130.04,129.82,129.05,128.75,128.73,128.53,128.34,128.31,128.20,128.08,128.01,81.99,79.24,77.59,76.84,75.07,74.61,72.78,72.61,68.38,31.11.HRMS(ESI)：C ₃₄ H ₃₆ NO ₆ [M+H] ⁺ Calculated values: 554.2537, found: 554.2549.

example IV-3 preparation of Compound IV-3

Compound II-8 (43.3 mg,0.1 mmol) was placed in a 10ml round bottom flask, dissolved in 30ml acetone, then added with 2M diethyl ether hydrochloride solution (100. Mu.l, 0.2 mmol), followed by 1 drop of purified water, stirred at room temperature for 1 day, and then a large amount of precipitate was separated out, and the white solid product, i.e., hydrochloride salt of IV-3, was obtained by suction filtration, 10.1mg in total, and the yield was 23%. ¹ H NMR(600MHz,MeOH-d ₄ )δ8.12–8.00(m,4H),5.57(q,J＝9.2Hz,1H),5.37–5.24(m,1H),5.18–5.11(m,1H),5.05(dd,J＝19.6,9.0Hz,1H),4.33–4.24(m,1H),4.20–4.12(m,2H),2.58(s,3H),1.99(s,9H). ¹³ C NMR(150MHz,MeOD4)δ198.08,170.63,169.87,169.68,164.87,140.98,132.16,129.94,129.59,128.14,126.41,79.31,74.51,71.91,71.21,67.30,61.22,25.64,19.18,19.09,18.96.HRMS(ESI)：C ₂₁ H ₂₆ NO ₁₀ [M+H] ⁺ Calculated values: 452.1551, found: 452.1555.

example IV-4 preparation of Compound IV-4

Compound IV-2 (55.3 mg,0.1 mmol) was placed in a 10ml round bottom flask and 5ml dichloromethane, 3 were addedAfter the triethylamine was dissolved, copper acetate (18.2 mg,0.1 mmol) and p-tolueneboronic acid (39 mg,0.3 mmol) were sequentially added to the reaction solution and stirred at room temperature for 2 days, the reaction solution was quenched with water (30 ml) after the TLC detection reaction took place, then extracted twice with ethyl acetate (15 ml), the organic phases were combined and washed twice with water, dried over anhydrous sodium sulfate, and the organic phases were evaporated under reduced pressure to dryness, and the silica gel plate was analyzed and separated to give a white solid product, 15.8mg in total, with a yield of 25%. ¹ H NMR (600 MHz, acetone-d) ₆ )δ8.06(dd,J＝8.4,1.4Hz,2H),7.66–7.61(m,1H),7.50(dd,J＝8.3,7.4Hz,2H),7.36–7.28(m,10H),7.16(m,5H),6.93–6.90(m,2H),6.74–6.70(m,2H),5.36(d,J＝9.9Hz,1H),5.22(t,J＝9.2Hz,1H),5.07(dd,J＝9.9,9.0Hz,1H),4.91–4.86(m,2H),4.75(dd,J＝27.2,11.1Hz,2H),4.62–4.53(m,2H),4.13(dd,J＝9.3,8.6Hz,1H),3.84–3.78(m,3H),2.16(s,3H). ¹³ C NMR (150 MHz, acetone-d) ₆ )δ165.32,143.42,138.31,138.27,138.07,132.85,129.10,128.87,128.13,127.77,127.70,127.61,127.39,127.23,127.22,127.05,126.93,126.84,113.94,83.34,83.28,78.17,75.29,74.51,74.07,73.68,72.44,68.65,19.14.HRMS(ESI)：C ₄₁ H ₄₂ NO ₆ [M+H] ⁺ Calculated values: 644.3007, found: 644.3010.

Example IV-5 preparation of Compound IV-5

IV-2 (55.3 mg,0.1 mmol) was placed in a 10ml round bottom flask, 5ml of tetrahydrofuran was added to dissolve, triethylamine (43.2. Mu.l, 0.3 mmol) and succinic anhydride (15 mg,0.15 mmol) were added sequentially to the reaction solution, and the mixture was stirred at room temperatureAfter completion of the reaction by tlc for 3h, the reaction was quenched with water (30 ml), then extracted twice with ethyl acetate (15 ml), the combined organic phases were washed twice with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure, then isolated as a white solid product by chromatography on silica gel plate, 60.3mg total, 92% yield. ¹ H NMR(400MHz,CDCl ₃ )δ8.04–7.94(m,2H),7.60(t,J＝7.4Hz,1H),7.45(t,J＝7.6Hz,2H),7.39–7.29(m,8H),7.22–7.08(m,7H),6.74(d,J＝9.1Hz,1H),5.29(t,J＝9.3Hz,1H),5.18(t,J＝9.2Hz,1H),4.81(dd,J＝10.9,8.0Hz,2H),4.77–4.63(m,2H),4.52(dd,J＝17.7,11.4Hz,2H),3.91(m,2H),3.78(s,1H),3.68–3.63(m,1H),2.61–2.31(m,4H). ¹³ C NMR(125MHz,CDCl ₃ )δ172.24,166.81,137.63,133.63,129.81,128.53,128.38,128.27,128.02,127.86,127.81,127.77,127.71,82.99, 78.38,75.43,75.06,73.55,73.52,67.95,30.71,29.66.HRMS(ESI)：C ₃₈ H ₃₉ NNaO ₉ [M+Na] ⁺ Calculated values: 676.2517, found: 676.2520.

example IV-6 preparation of Compound IV-6

IV-2 (55.3 mg,0.1 mmol) was placed in a 10ml round bottom flask, after adding 5ml of methylene chloride, triethylamine (43.2. Mu.l, 0.3 mmol), N-BOC-L-aspartic acid-1-methyl ester (36 mg,0.15 mmol) and HATU (76 mg,0.2 mmol) were added sequentially to the reaction solution, stirred at room temperature for 6h, after completion of TLC detection the reaction solution was quenched with water (30 ml) followed by extraction twice with ethyl acetate (15 ml), the organic phases were combined and washed twice with water, dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure, followed by analytical separation on silica gel to give a white solid product in a total of 57.1mg, yield 73%. ¹ H NMR(500MHz,CDCl ₃ )δ8.0–8.0(m,2H),7.6(ddt,J＝8.7,7.1,1.3Hz,1H),7.5–7.4(m,2H),7.4–7.3(m,10H),7.2–7.1(m,8H),6.7(d,J＝9.2Hz,1H),5.7(d,J＝8.9Hz,1H),5.3(t,J＝9.3Hz,1H),5.2(t,J＝9.3Hz,1H),4.9–4.8(m,2H),4.7(d,J＝11.1Hz,1H),4.7(s,1H),4.6(d,J＝10.8Hz,1H),4.5(d,J＝12.0Hz,1H),4.5–4.4(m,1H),3.9(dt,J＝29.3,9.1Hz,2H),3.8–3.8(m,2H),3.6–3.6(m,1H),3.3(s,3H),2.8–2.8(m,1H),2.7(dd,J＝16.5,4.4Hz,1H),1.4(s,9H). ¹³ C NMR(125MHz,CDCl ₃ )δ171.4,170.7,166.7,155.6,137.8,137.7,137.7,133.6,129.9,129.1,128.5,128.4,128.3,128.0,127.9,127.9,127.8,127.8,83.0,80.0,78.3,77.5,76.7,75.5,75.1,73.6,73.6,68.0,52.1,50.8,49.8,37.8,28.3.HRMS(ESI)：C ₄₄ H ₅₁ N ₂ O ₁₁ [M+H] ⁺ Calculated values: 783.3487, found: 783.3499.

the following are examples of the preparation of compounds of formula V:

example V-1 preparation of Compound V-1

Compound III-1 (33.1 mg 0.1 mmol) was dissolved in a dry round bottom flask containing 3ml of dry dichloromethane, followed by addition of boron trifluoride etherate (20 μl), nitrogen protection for 12 hours, quenched by addition of deionized water (20 ml) after the reaction was completed, and the reaction was extracted twice with ethyl acetate (20 ml). Will thenThe organic phases were combined and washed once with deionized water (30 ml), washed once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated using a rotary evaporator and dissolved in dichloromethane, followed by column chromatography on silica gel (PE: ea=2:1) to give the product as a grey oil. Total 28mg, yield 95%. ¹ H NMR(400MHz,CDCl ₃ )δ7.87(m,2H),7.60–7.52(m,1H),7.47(dd,J＝8.4,7.0Hz,2H),7.23(d,J＝7.4Hz,1H,NH),7.04(dd,J＝10.3,1.6Hz,1H),6.33(dd,J＝10.3,2.8Hz,1H),5.91(dd,J＝7.5,2.0Hz,1H),4.98(s,1H),4.42(dd,J＝11.8,5.2Hz,1H),4.26(dd,J＝11.8,4.3Hz,1H),2.10(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ190.86,170.66,167.53,148.37,133.02,132.41,128.70,127.70,127.40,78.74,73.28,64.65,20.77.HRMS(ESI):C ₁₅ H ₁₆ NO ₅ [M+H] ⁺ Calculated 290.1023, found 290.1027.

Example V-2 preparation of Compound V-2

Compound III-1 (33.1 mg,0.1 mmol) was dissolved in a dry round bottom flask containing 3ml of dry dichloromethane, followed by N-bromosuccinimide (NBS) (18 mg,0.1 mmol), nitrogen-protected for 12 hours, quenched by the addition of deionized water (20 ml) after the reaction was completed, and the reaction was extracted twice with ethyl acetate (20 ml). The organic phases were then combined and washed once with deionized water (30 ml), washed once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated using a rotary evaporator and dissolved in dichloromethane, and chromatographed on silica gel (PE: ea=2:1) to give 25.5mg of the product as a yellow oil in 72% yield. ¹ H NMR(500MHz,CDCl ₃ )δ7.92–7.86(m,2H),7.62–7.57(m,1H),7.53–7.48(m,2H),7.45(d,J＝1.8Hz,1H),7.26(d,J＝7.7Hz,1H,NH),6.04(dd,J＝7.7,2.0Hz,1H),4.98(m,1H),4.43(dd,J＝11.8,5.2Hz,1H),4.27(dd,J＝11.8,4.8Hz,1H),2.14(s,3H). ¹³ C NMR(150MHz,CDCl ₃ )δ185.04,170.53,167.36,148.52,132.73,132.61,128.79,127.42,120.57,79.25,74.03,64.18,20.77.HRMS(ESI):C ₁₅ H ₁₅ BrNO ₅ [M+H] ⁺ Calculated 368.0128, found 368.0117.

Example V-3 preparation of Compound V-3

Compound III-1 (33.1 mg 0.1 mmol) was dissolved in a dry round bottom flask containing 3ml of dry dichloromethane, followed by addition of iodine monochloride (1 ml,10 eq) and nitrogen protection for 12 hours, after the reaction was completed, the reaction was quenched by addition of saturated sodium thiosulfate (20 ml) and the reaction solution was extracted twice with ethyl acetate (20 ml). The organic phases were then combined and washed once with deionized water (30 ml), once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated using a rotary evaporator and dissolved in dichloromethane, and chromatographed on silica gel (PE: ea=2:1) to give 28.1mg of a yellow solid in 68% yield. ¹ H NMR(500MHz,CD ₂ Cl ₂ )δ7.92–7.85(m,2H),7.78(d,J＝1.8Hz,1H),7.66–7.57(m,1H),7.56–7.51(m,2H),7.31(d,J＝7.5Hz,1H),6.06(dd,J＝7.8,1.8Hz,1H),5.02(m,1H),2.12(s,3H). ¹³ C NMR(125MHz,CD ₂ Cl ₂ )δ185.95,170.33,166.99,156.77,132.96,132.44,128.73,127.30,97.66,78.20,75.50,64.01,20.48.HRMS(ESI):C ₁₅ H ₁₅ INNaO ₅ [M+Na] ⁺ Calculated 437.9809, found 437.9814.

Example V-4 preparation of Compound V-4

Compound III-22 (41.6 mg 0.1 mmol) was dissolved in a dry round bottom flask containing 3ml of dry dichloromethane, followed by addition of boron trifluoride etherate (20 μl), nitrogen protection for 12 hours, quenched by addition of deionized water (20 ml) after the reaction was completed, and the reaction was extracted twice with ethyl acetate (20 ml). The organic phases were then combined and washed once with deionized water (30 ml), once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate and filtered. After spin-drying using a rotary evaporator, the mixture was redissolved in dichloromethane, stirred on silica gel and separated by column chromatography on silica gel pe:ea=2:1 to give the product as a yellow oil. Together 30.5mg, 92% yield. ¹ H NMR(500MHz,CDCl3)δ7.90–7.83(m,2H),7.59–7.51(m,1H),7.46(dd,J＝8.3,7.0Hz,2H),7.23(d,J＝7.5Hz,1H),7.04(dd,J＝10.3,1.6Hz,1H),6.32(dd,J＝10.3,2.8Hz,1H),5.90(dd,J＝7.5,2.0Hz,1H),4.97(s,1H),4.46(dd,J＝11.7,5.1Hz,1H),4.21(dd,J＝11.7,4.9Hz,1H),1.20(s,9H). ¹³ C NMR(125MHz,CDCl3)δ190.93,178.07,167.52,148.65,133.10,132.35,128.68,127.42,127.39,78.72,73.40,64.28,27.11.LRMS(ESI):C ₁₈ H ₂₁ NO ₅ [M+H]+found 332.4.

The following are examples of the preparation of compounds of formula VI:

example VI-1 preparation of Compound VI-1

Compound III-1 (66.2 mg, 0.2 mmol) was dissolved in a buffer solution containing 3ml of PH=8, followed by addition of methyl (R) -2-acetamido-3-mercaptopropionate (17.2 mg,0.1 mmol), stirring for 12 hours, dilution with deionized water (20 ml) after completion of the reaction, and extraction of the reaction solution with ethyl acetate (20 ml) twice. The organic phases were then combined and washed once with deionized water (30 ml), washed once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated on a rotary evaporator and dissolved in dichloromethane, followed by column chromatography on silica gel (DCM: meoh=15:1) to give 31.6mg of the product as a yellow oil in 68% yield. ¹ H NMR(500MHz,CDCl ₃ )δ7.84–7.81(m,2H),7.56–7.51(m,1H),7.45(t,J＝7.7Hz,2H),7.27(d,1H),6.44(d,J＝7.2Hz,1H),5.75(d,J＝7.8Hz,1H),4.82(m,1H),4.50(dd,J＝12.2,2.2Hz,1H),4.43–4.38(m,1H),4.14–4.09(m,1H),3.78(s,3H),3.29–3.09(m,4H),3.01(dd,J＝13.8,5.2Hz,1H),2.71(dd,J＝14.6,12.3Hz,1H),2.11(s,3H),2.07(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ198.63,170.86,170.12,167.23,132.88,132.47,128.71,127.40,80.54,78.08,63.47,52.96,52.09,45.40,43.76,33.01,23.07,20.85.HRMS(ESI):C ₂₁ H ₂₇ N ₂ O ₈ S[M+H] ⁺ Calculated 467.1483, found 467.1474.

Example VI-2 preparation of Compound VI-2

The experimental operation is same as that of VI-1, the sulfhydryl substrate is changed into customized pentapeptide, the reaction liquid mass spectrum is taken to monitor the reaction completely, and the molecular weight of the VI-2 compound and the ESI-MS are obviously seen: 953.5[ M+H ]] ⁺ The mass spectrum is shown in figure 3.

Example VI-3 preparation of Compound VI-3

The experimental operation is the same as that of VI-1, the sulfhydryl substrate is replaced by cysteine-somatotropin releasing peptide, the reaction liquid mass spectrum is taken to monitor the reaction completely, and the molecular weight of the VI-2 compound and ESI-MS are obviously seen: 1068.6[ M+H ] ] ⁺ The mass spectrum is shown in fig. 4.

The following are other compound preparation examples:

example VII-1 preparation of Compound VII-1

Compound IV-2 (55.3 mg,0.1 mmol) was placed in a 10ml round bottom flask, followed by the sequential addition of acetone (5 ml), 10 drops of 12M hydrochloric acid, and sodium nitrite (13 mg,0.2 mmol) after the solution was stirred well. The reaction was carried out at room temperature overnight. After completion of the TLC monitoring reaction, the reaction mixture was quenched with water (30 ml), extracted twice with ethyl acetate (20 ml), the organic phases were combined, washed twice with water, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure, followed by separation using a silica gel plate to give 45.1mg of a white solid product in 81% yield. ¹ H NMR(500MHz,CDCl ₃ )δ8.13–8.01(m,2H),7.59(t,J＝7.4Hz,1H),7.47(d,J＝7.8Hz,2H),7.40–7.29(m,11H),7.21–7.17(m,4H),5.58(t,J＝3.3Hz,1H),5.16(dd,J＝10.0,3.5Hz,1H),4.90–4.82(m,3H),4.64(d,J＝12.4Hz,1H),4.59–4.55(m,2H),4.27(t,J＝9.5Hz,1H),4.18(dt,J＝10.2,3.5Hz,1H),3.76–3.70(m,3H),3.11(d,J＝3.5Hz,1H). ¹³ C NMR(125MHz,CDCl ₃ )δ138.13,138.01,137.82,133.25,129.88,129.82,128.46,128.42,128.41,128.32,128.00,127.95,127.91,127.79,127.76,127.65,90.64,79.69,78.14,75.56,75.12,74.20,73.54,70.43,68.78.HRMS(ESI)：C ₃₄ H ₃₈ NO ₇ [M+NH ₄ ] ⁺ Calculated values: 572.2643, found: 572.2628.

example VII-2 preparation of Compound VII-2

Compound II-24 (55 mg,0.1 mmol) was dissolved in 5ml DMF, copper powder (64 mg,1.0 mmol) was added, stirred well and heated to 120℃for 4h, the reaction mixture was quenched with 20ml water, extracted twice with 15ml ethyl acetate, the organic phases were combined and washed once with water, washed once with saturated sodium chloride, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to give 38.0mg of the product as a colourless oil in 40% yield. ¹ H NMR(500MHz,CDCl ₃ )δ7.29(s,1H),5.79(d,J＝7.6Hz,2H),4.93–4.85(m,4H),4.28(m,4H),4.06(m,2H),3.98(s,12H),3.96(s,2H),3.73(s,6H),2.09(s,6H),2.08(s,6H),1.99(s,6H). ¹³ C NMR(125MHz,CDCl ₃ )δ170.63,169.52,169.24,166.93,152.88,151.96,121.16,108.46,92.58,71.78,67.53,67.47,62.73,60.88,60.56,56.21,20.74,20.59.HRMS(ESI)：C ₄₄ H ₅₃ N ₂ O ₂₂ [M+H] ⁺ Calculated values: 961.3084, found: 961.3092.

Example VII-3 preparation of Compound VII-3

Compound II-1 (1.5 g,3.83 mmol) was placed in a 100ml round bottom flask, 50ml of methanol was added to dissolve, triethylamine (2.5 ml of 5 eq) was added, stirring was carried out for 2 days, TLC detection of the completion of the reaction of the starting material was followed by spin-drying the reaction solution to give an oily product, 30ml of dry acetonitrile was added to dissolve, then benzaldehyde (2 ml,2 eq) and p-toluenesulfonic acid ((3.5 g,2 eq) were added in sequence, nitrogen protection was carried out for 6 hours, after TLC detection of the completion of the reaction, the reaction solution was diluted with deionized water (50 ml) and extracted twice with ethyl acetate (50 ml), the organic phases were combined and washed twice (50 ml) with water, saturated sodium chloride (50 ml) was washed once, dried over anhydrous sodium sulfate, evaporated to dryness under reduced pressure, dichloromethane was added to redissolve and stirred with silica gel, and the product was separated by column chromatography to give a yellow oily product in a total of 1.06g, yield 79%. ¹ H NMR(600MHz,CDCl ₃ )δ8.07–8.02(m,2H),7.47(dd,J＝6.7,3.3Hz,4H),7.42–7.35(m,4H),6.05(d,J＝8.0Hz,1H),5.60(d,J＝6.7Hz,1H),4.69(dd,J＝8.0,5.7Hz,1H),4.46(dd,J＝10.4,4.9Hz,1H),3.94(dd,J＝9.6,5.7Hz,1H),3.82–3.70(m,2H),3.59(t,J＝9.4Hz,1H). ¹³ C NMR(150MHz,CDCl ₃ )δ164.35,136.47,131.98, 129.46,128.90,128.19,128.06,127.90,126.31,125.76,101.50,94.87,80.19,78.11,74.32,68.24,62.58,29.23.HRMS(ESI)：C ₂₀ H ₂₀ N O ₅ [M+H]+calculated value: 354.1336, found: 354.1335.

example VII-4 preparation of Compound VII-4

Compound VII-3 (45 mg,1 mmol) was dissolved in 5ml dry DMF, nitrogenBenzyl bromide (30 μl,2 eq) and NaH (12 mg,2 eq) were added in sequence, stirred at room temperature for 30 min, after TLC monitoring the reaction was complete, the reaction solution was quenched with deionized water (20 ml), extracted twice with ethyl acetate (20 ml), the organic phases were combined, washed twice with water (2 ml), once with saturated sodium chloride (20 ml), dried over anhydrous sodium sulfate, evaporated to dryness under reduced pressure, redissolved with dichloromethane and stirred with silica gel, and the column chromatography was carried out to give a yellow solid product, 42.1mg total, yield 95%. ¹ H NMR(500MHz,CDCl ₃ )δ7.98–7.91(m,2H),7.59–7.52(m,1H),7.51–7.42(m,5H),7.42–7.27(m,7H),6.06(d,J＝8.1Hz,1H),5.64(s,1H),4.94–4.84(m,2H),4.77(dd,J＝8.1,4.6Hz,1H),4.44(dd,J＝10.6,5.2Hz,1H),3.86–3.73(m,3H),3.66(m,1H). ¹³ C NMR(125MHz,CDCl ₃ )δ164.83,132.39,128.99,128.62,128.47,128.41,128.20,128.03,127.82,126.07,101.34,95.35,80.74,80.62,78.85,73.20,68.83,62.85.HRMS(ESI)：C ₂₇ H ₂₆ N O ₅ [M+H]+calculated value: 444.1805, found: 444.1815.

example VII-5 preparation of Compound VII-5

Compound VII-4 (45 mg,0.1 mmol) was placed in a 10ml round bottom flask, acetone (3 ml) was added to dissolve, then 2M ethereal hydrochloride (0.25 ml) and water (25. Mu.L) were added, stirring overnight at room temperature after dissolving, after TLC monitoring the reaction was complete the reaction was evaporated to dryness under reduced pressure, the residue was washed 3 times with dichloromethane and filtered to give 35.2mg of a yellow solid product in 94% yield. ¹ H NMR(500MHz,DMSO-d ₆ )δ8.97(s,2H),7.97(d,J＝7.6Hz,2H),7.69(t,J＝7.3Hz,1H),7.55(t,J＝7.7Hz,2H),7.18–7.12(m,1H),7.12–7.03(m,4H),5.80(s,1H),5.06(t,J＝9.2Hz,1H),4.87(d,J＝9.0Hz,1H),4.81(d,J＝11.5Hz,1H),4.56(d,J＝11.5Hz,1H),3.83–3.74(m,2H),3.62–3.49(m,5H). ¹³ C NMR(125MHz,DMSO-d6)δ164.98,138.17,133.52,129.61,129.57,128.57,127.93,127.45,127.35,81.75,79.48,78.96, 73.98,71.90,69.53,60.01.HRMS(ESI)：C ₂₀ H ₂₄ NO ₆ [M+H] ⁺ Calculated 374.1598, found 374.1596.

Claims

An oxazoline saccharide compound represented by formula I:

wherein,
is a double bond or a single bond;

n is 0 or 1, in particular 1;

R ¹ 1 or 2 substituents on the A ring selected from unsubstituted or hydroxy, C1-C6 alkanoyloxy, C6-C12 aralkoxy or C6-C12 aryloxy substituted C1-C6 alkyl, unsubstituted or C1-C6 alkyl substituted C1-C6 alkanoyloxy, unsubstituted or C6-C12 aryl substituted C1-C6 alkoxy, unsubstituted or C1-C6 alkyl substituted C6-C12 aryloxy, unsubstituted or C1-C6 alkyl substituted C6-C12 aralkoxy, hydroxy, monoglycosyloxy, disaccharideyloxy, oligosaccharyloxy, polysaccharyloxy, hydrogen; preferably, R ¹ 1 or 2 substituents on the A ring selected from unsubstituted or hydroxy, C1-C6 alkanoyloxy, C6-C12 aralkoxy or C6-C12 aryloxy substituted C1-C3 alkyl, unsubstituted or C1-C3 alkyl substituted C1-C3 alkanoyloxy, unsubstituted or C6-C12 aryl substituted C1-C3 alkoxy, unsubstituted or C1-C3 alkyl substituted C6-C12 aryloxy, unsubstituted or C1-C3 alkyl substituted C6-C12 aralkoxy, hydroxy, monoglycosyloxy, disaccharideyloxy, hydrogen;

R ² Selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted 5-to 9-membered heteroaryl, wherein the substituent of the C6-C12 aryl group is selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, halogen, halo C1-C6 alkyl, C1-C6 alkanoyl1, 2, 3 or 4 substituents in the group, C2-C6 alkynyl, phenyl, or two adjacent substituents on the C6-C12 aryl group together with the attached aryl carbon atom form a 5-9 membered heterocyclic group, the substituents of the 5-9 membered heteroaryl group being halogen; preferably, 1, 2, 3 or 4 substituents selected from C1-C6 alkyl, C3-C6 cycloalkyl, naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-9 membered heteroaryl, wherein the phenyl substituent is selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, halogenated C1-C3 alkyl, C1-C6 alkanoyl, C2-C6 alkynyl, phenyl, or two adjacent substituents on phenyl together with the attached phenyl carbon atom form a 5-9 membered heterocyclyl, the 5-9 membered heteroaryl substituent is halogen;

R ³ selected from the group consisting of hydrogen, C1-C6 alkanoyloxy, C1-C6 alkyl substituted or unsubstituted C6-C12 aralkyloxy, C1-C6 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C6 alkoxy, hydroxy, monoglycosyloxy, disaccharideyloxy, oligosaccharyloxy, polysaccharide yloxy; preferably, hydrogen, C1-C6 alkanoyloxy, C1-C3 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C6 alkoxy;

R ⁴ Selected from hydrogen, hydroxy, C1-C6 alkanoyloxy, C1-C6 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C6 alkoxy; preferably, hydrogen, hydroxy, C1-C6 alkanoyloxy, C1-C3 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C3 alkoxy;

q is O, N or S;

w is O, N or S.
The oxazoline saccharide compound represented by the formula I or a pharmaceutically acceptable salt thereof according to claim 1, wherein,

is a double bond or a single bond;

n is 0 or 1;

R ¹ 1 or 2 substituents on the A ring selected from the group consisting of C1-C3 alkyl, benzyloxy C1-C3 alkyl, hydroxy C1-C3 alkyl, C1-C6 alkanoyloxy C1-C3 alkyl, C6-C12 aralkoxy C1-C3 alkyl, C1-C3 alkyl C1-C3 alkanoyloxy, C1-C3 alkoxy, C6-C12 aryloxy, C6-C12 aralkoxy, hydroxy, monoglycosyloxy, disaccharide acyloxy, benzyloxy, hydrogen;

R ² a substituent selected from the group consisting of C1-C3 alkyl, C3-C5 cycloalkyl, naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-to 9-membered heteroaryl, wherein the substituent for phenyl is 1, 2, 3 or 4 substituents selected from the group consisting of C1-C3 alkyl, C1-C3 alkoxy, halogen, trifluoromethyl, C1-C3 alkanoyl, C2-C4 alkynyl, phenyl, or two adjacent substituents on phenyl together with the attached phenyl carbon atom form dioxolane, and the substituent for 5-to 9-membered heteroaryl is selected from F, cl, br, I;

R ³ Selected from hydrogen, C1-C6 alkanoyloxy, C1-C6 alkoxy, C6-C12 aralkyloxy;

R ⁴ selected from hydrogen, hydroxy, C1-C6 alkanoyloxy, C1-C6 alkoxy, C6-C12 aralkyloxy;

q is O;

w is O.
The oxazoline saccharide compound represented by the formula I or a pharmaceutically acceptable salt thereof according to claim 1, wherein,

is a double bond or a single bond;

n is 0 or 1;

R ¹ is 1 or 2 substituents on ring A selected from the group consisting of acetoxymethyl, pentanoyloxymethyl, benzoyloxymethyl, benzyloxymethyl, acetoxy, pentanoyloxy, benzoyloxy, methyl, ethyl, hydroxy, hydroxymethyl, monoglycosyloxy, disaccharideyloxy, benzyloxy andhydrogen;

R ² selected from methyl, ethyl, naphthyl, substituted or unsubstituted phenyl, and substituted or unsubstituted 5-9 membered heteroaryl, wherein the phenyl is 1, 2, 3, or 4 substituents selected from methyl, ethyl, methoxy, ethoxy, F, cl, br, I, trifluoromethyl, acetyl, ethynyl, phenyl, and the 5-9 membered heteroaryl is selected from benzodioxolyl, thienyl, and furyl, and the substituents are selected from F, cl, br, I;

R ³ selected from the group consisting of hydrogen, acetoxy, pentanoyloxy, benzoyloxy and benzyloxy;

R ⁴ Selected from the group consisting of hydrogen, hydroxy, acetoxy, pentanoyloxy, benzoyloxy, and benzyloxy;

q and W are O.
The oxazoline saccharide compound represented by the formula I or a pharmaceutically acceptable salt thereof according to claim 1, wherein the compound of the formula I is a compound of the following formula II or formula III

Wherein n, R ¹ ，R ² ，R ³ ，R ⁴ W and Q are as defined in claim 1.
The oxazoline saccharide compound represented by formula I or a pharmaceutically acceptable salt thereof according to claim 1, wherein the compound of formula I is a compound of the following formula I:
a process for preparing an oxazoline saccharide compound represented by formula I of claim 1, which comprises:

the compound 1 and the compound 2 are in a solvent S to generate a compound shown in a formula I under the action of A,

route one

Specifically, the method includes the following methods shown in route two and route three:

as shown in scheme two, compound 1 and compound 2 in solvent S1 in the presence of A1 to form compound II;

as shown in scheme three, compound 1 and compound 2 in solvent S2 in the presence of A2 to form compound III;

route two

Route three

Wherein n, R ¹ ，R ² ，R ³ ，R ⁴ W and Q are as defined in claim 1, R ⁵ And R is ⁶ Selected from the group consisting of substituted or unsubstituted C1-C6 alkanoyl, substituted or unsubstituted C6-C12 aroyl, substituted or unsubstituted C6-C12 aryl, and C1-C6 alkyl, wherein the substituents for substitution are selected from the group consisting of halogen, C1-C6 alkyl, and C1-C6 alkoxy; u is defined as W;

Wherein A, A, A2 are lewis acids, protic acids, or a combination of lewis acids and protic acids;

the solvents S, S, S2 are aprotic solvents, protic solvents, or a combination of aprotic and protic solvents.
Use of an oxazoline saccharide compound of formula I according to claim 1 for specific modification of different sites on the saccharide ring for the flexible assembly of oligosaccharides and glycopeptides; and the use of thiol groups for the detection of sulfur-containing molecules and for the specific modification of peptides or proteins.
The use according to claim 7, wherein the compound of formula I is a compound of formula II or III

The use comprises the synthesis of the following compounds of formula IV, formula V or formula VI from compounds of formula II or formula III, including the following routes four, five, six:

route four

After reaction of compound II with acid, R is generated ⁸ Is a combination of hydrogenCompound IV, then reacted with carboxylic acid compounds, anhydrides, acid chloride compounds or halogenated compounds to convert R ⁸ A compound IV which is not hydrogen;

wherein n, R ¹ ，R ² ，R ³ W and Q are as defined in claim 1, R ⁸ Is hydrogen, p-tolyl, 1-carboxyethyl-4-carbonyl, p-methoxyphenylcarbonyl, methyl 2- (tert-butoxycarbonylamino) valerate 4-carbonyl;

In the method of synthesizing the compound of formula IV, the acid comprises a protic acid, a lewis acid, or a combination thereof;

route five

Wherein R is ¹ ，R ² ，R ⁴ W and Q are as defined in claim 1, X is hydrogen or halogen;

when X is hydrogen, compound V can be obtained from compound III by reaction with water in the presence of an acid (scheme five);

when X is halogen, compound V is obtainable by reacting compound III with a halogenating agent (scheme five);

route six

Reacting the compound III with a sulfhydryl-containing compound to convert the compound III into a compound VI;

wherein R is ¹ ，R ² ，R ⁴ W and Q are as defined in claim 1, R ⁷ Selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C12 aryl, cysteine residue containing oligopeptides or polypeptides or proteins, wherein the substituents for substitution are selected from halogen, C1-C6 alkyl, C1-C6 alkoxy.
A compound prepared from a compound of formula I according to claim 1, as follows:

wherein n, R ¹ ，R ² ，R ³ W and Q are as defined in claim 1; r is R ⁷ Selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C12 aryl, cysteine residue-containing oligopeptides or polypeptides or proteins, wherein the substituents for substitution are selected from halogen, C1-C6 alkyl, C1-C6 alkoxy; r is R ⁸ Is hydrogen, p-tolyl, 1-carboxyethyl-4-carbonyl, p-methoxyphenylcarbonyl, methyl 2- (tert-butoxycarbonylamino) valerate 4-carbonyl, X is hydrogen or halogen.
A compound prepared from a compound of formula I according to claim 1, as follows: