GB2122600A - Hexahydronaphthacene derivatives - Google Patents
Hexahydronaphthacene derivatives Download PDFInfo
- Publication number
- GB2122600A GB2122600A GB8312388A GB8312388A GB2122600A GB 2122600 A GB2122600 A GB 2122600A GB 8312388 A GB8312388 A GB 8312388A GB 8312388 A GB8312388 A GB 8312388A GB 2122600 A GB2122600 A GB 2122600A
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- GB
- United Kingdom
- Prior art keywords
- cis
- benzeneboronate
- dioxo
- hexahydro
- naphthacenediyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- XHILBYYDFPCXTK-UHFFFAOYSA-N 1,2,3,4,4a,5-hexahydrotetracene Chemical class C1=CC=C2C=C(CC3C(CCCC3)=C3)C3=CC2=C1 XHILBYYDFPCXTK-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 125000002252 acyl group Chemical group 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 5
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 37
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- YXRWSFRRQBFSQF-UHFFFAOYSA-N O1C(C2=CC3=CC4=CC=CC=C4C=C3C=C2C=C2)=C2OB1C1=CC=CC=C1 Chemical compound O1C(C2=CC3=CC4=CC=CC=C4C=C3C=C2C=C2)=C2OB1C1=CC=CC=C1 YXRWSFRRQBFSQF-UHFFFAOYSA-N 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- 239000000543 intermediate Substances 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract 2
- 239000001257 hydrogen Substances 0.000 abstract 2
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 230000003115 biocidal effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 230000003647 oxidation Effects 0.000 description 9
- 238000007254 oxidation reaction Methods 0.000 description 9
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229940117975 chromium trioxide Drugs 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- -1 substituted-phenyl Chemical group 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/26—Radicals substituted by doubly bound oxygen or sulfur atoms or by two such atoms singly bound to the same carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Compounds of the formulae <IMAGE> and <IMAGE> in which R<1> is lower alkyl, esterified carboxy, a group <IMAGE> where R<2> and R<3> together are oxo or protected oxo and X is hydrogen, hydroxy or acyloxy, or a group -(CH2)n-OY, where n is 1 or 2 and Y is hydrogen, alkyl or acyl; Ar is aryl; and R<4> is acyl, are useful as intermediates for the manufacture of tetracyclic compounds having antibiotic or antitumour activity.
Description
SPECIFICATION
Hexahydronaphthacene derivatives
The present invention is concerned with hexahydronaphthacene derivatives.
The hexahydronaphthacene derivatives provided by the present invention are compounds of the general formulae
wherein R1 represents a lower alkyl or esterified carboxy group or a group of the formula
in which R2 and R3 together form an oxo group or a protected oxo group and X represents a hydrogen atom or a hydroxy or acyloxy group, or (CH2)n -OY b in which n stands for 1 or 2 and Y represents a hydrogen atom or an alkyl or acyl group, Ar represents an aryl group and R4 represents an acyl group.
The compounds of formulae la and Ib are useful intermediates in the process described in our copending
Application No. 8023715.
As used in this Specification, the term "lower alkyl" means a straight-chain or branched-chain alkyl group which preferably contains from 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, tert.
butyl, pentyl, hexyl etc. A protected oxo group herein can be any conventional protected oxo group.
Preferably, an oxo group is protected in the form of a ketal or thioketal, especially an alkylene ketal or alkylene thioketal. An esterified carboxy group can be an alkoxycarbonyi group (e.g. methoxycarbonyl, ethoxycarbonyl etc), an aryloxycarbonyl group (e.g. phenoxycarbonyl etc) or an arylkoxycarbonyl group (e.g. benzyloxycarbonyl etc). The methoxycarbonyl group is the preferred alkoxycarbonyl group. An acyl group or the acyl moiety of an acyloxy group can be derived from an alkanecarboxylic acid (e.g. acetic acid, propionic acid etc), an aromatic carboxylic acid (e.g. benzoic acid etc) or an araliphatic carboxylic acid (e.g.
phenylacetic acid etc). An aryl group can be, for example, phenyl, substituted-phenyl (e.g. methoxyphenyl), pyridyl etc.
The compounds of formula la hereinbefore can be prepared by de-acylating a compound of formula Ib herein before.
The de-acylation of a compound of formula Ib is preferably carried out using boron trichloride in an inert organic solvent (e.g. a halogenated hydrocarbon such as dichloromethane etc) and at a low temperature (e.g. at about -100C). The de-acylation may also be carried out by aqueous acid or base treatment under conventional conditions.
The compounds of formula Ib hereinbefore can be prepared by oxidising a compound of the general tormula
,wherein R1, R4 and Ar have the significance given earlier, with a chromic oxidising agent under anhydrous conditions.
A preferred chromic oxidising agent for use in the foregoing oxidation is chromium trioxide. In a preferred embodiment, this oxidation is carried out in the presence of a mixture of an appropriate anhydrous carboxylic acid and the anhydride corresponding thereto (e.g. a mixture of glacial acetic acid and acetic anhydride). This oxidation can be carried out at a temperature between about room temperature and about 60"C, preferably at about room temperature.
The compounds of formula II hereinbefore are claimedperse in copending Application No.
Compounds of formulae la and Ib hereinbefore can exist not only in racemic but also in optically active form. It will be appreciated that the invention includes not only the racemates but also the optical isomers. A racemate can be split up into its optical isomers in accordance with methods known per se. For example, a compound in which R1 represents an esterified carboxy group can be saponified to the corresponding carboxylic acid (e.g. by treatment with an alkali metal hydroxide such es sodium hydroxide) and the acid can be resolved by salt formation with an appropriate base such as brucine. An optically active acid thus obtained can subsequently be esterified to give a corresponding optically active ester.
The following Examples illustrate the manner in which the compounds of formulae la and Ib can be prepared.
Example 1
(A) 331 mg (0.6 mmol) of rac-cisd,l 2-diacetoxy-3-(l,l-ethylenedioxyethyl)-l ,2,3,4-tetrahydro-l,3- naphthacene-diyl benzeneboronate were dissolved in a mixture of 18 ml of glacial acetic acid and 6 ml of acetic anhydride. 250 mg (2.4 mmol) of finely ground chromium trioxide were added and the mixture was stirred at room temperature for 16 hours. The mixture was then poured into 250 ml of water and the resulting suspension was extracted with two 200 ml portions of dichloromethane.The combined dichloromethane extracts were evaporated and the residue was triturated with diethyl ether and filtered to give 110 mg of rac-cis-5,1 2-diacetoxy-3-(1 , 1 -ethylenedioxyethyl)-1 ,2,3,4,6,1 1 -hexahydro-6,1 1 -dioxo-1 ,3-naphthacenediyl benzeneboronate in the form of a pale yellow solid of melting point 210 -220 C. Concentration of the diethyl ether mother liquor gave a second crop weighing 100 mg. The total yield of product was 210 mg (60%).
(B) Asolution of 100 mg (0.17 mmol) of rac-cis-5,12-diacetoxy-3-(1,1-ethylenedioxyethyl)1,2,3,4,6,11- hexa-hydro-6,1 1-dioxo-1 ,3-naphthacenediyl benzeneboronate in 20 ml of dichloromethane was stirred and cooled to -78 C. A solution of 125 mg of boron trichloride in 5 ml of dichloromethane was added and the mixture was stirred and left to warm to - 10 C over a period of 1 hour. The mixture was then poured into 20 ml of ice-cold 2-M hydrochloric acid and the layer were separated. The organic layer was washed with 20 ml of water, dried over an hydros sodium sulphate, filtered and the filtrate was evaporated.The residue was triturated with 5 ml of diethyl ether and filtered to give 60 mg (77%) of rac-cis-3-acetyl-1,2,3,4,6,11- hexahydro-5,1 2-dihydroxy-6,1 1 -dioxo-1 ,3-naphthacenediyl benzeneboronate in the form of a bright red solid of melting point 215 -223 C.
Example 2
(A) Oxidation of (1 R)-cis-5,1 2-diacetoxy-3-acetyi-1,2,3,4-tetrahydro-1,3-naphthacenediyl benzeneboron ate in a manner analogous to that described in Example 1 (A) yielded (1 R)-cis-5,12-diacetoxy-3-acetyl 1,2,3,4,6,11 -hexahydro-6,1 1 -dioxo-1 ,3-naphthacenediyl benzeneboronate in the form of off-white crystals of melting point 194 -199 C; [D20 = -173.3 (c = 0.5% in dioxan).
(B) (1 R)-cis-5,1 2-diacetoxy-3-acetyl-1 ,2,3,4,6,1 1 -hexahydro-6,1 1 ,dioxo-1 ,3-naphthacenediyl benzeneboronate was treated with boron trichloride in a manner analogous to that described in Example 1(B) to give (1 R)-cis-3-acetyl-1,2,3,4,6,11 -hexahydro-5,1 2-dihydroxy-6,1 1 -dioxo-1,3-naphthacenediyl benzeneboronate in the form of orange crystals of melting point 223 -224 C; [a]02c = -350.4 (c = 0.1% in dioxan).
Example 3
(A) (1R)-cis-5,12-diacetoxy-3-(1,1-ethylenedioxyethyl)-1,2,3,4-tetrahydro-1,3-nachthacenediyl benzeneboronate was oxidised in a manner analogous to that described in Example 1(A) to give (1 R)-cis-5,1 2- diacetoxy-3-(1,1-ethylenedioxyethyl)-1,2,3,4,6,11-hexahydro-6,11-dioxo-1,3-naphthacenediyl benzeneboronate which was used without further purification.
(B) Treatment of (1 R)-cis-5,1 2-diacetoxy-3-(1,1-ethylenedioxyethyl)-1,2,3,4,6,11 -hexahydro-6,1 1 -dioxo1,3-naphthacenediyl benzeneboronate with boron trichloride in a manner analogous to that described in
Example 1 (B) yielded (1 R,3R)-cls-3-aceWl-1 2,3,4,6,11 -hexahydro-5,1 2-dihydroxy-6,1 1 -dioxo-1 3- naphthacenediyl benzeneboronate which was identical with the product obtained according to Example 2(B).
Example 4
(A) Oxidation of (1 S)-cis-5,1 2-diacetoxy-3-acetyl-1 ,2,3,4-tetra hyd ro-1,3-na phthacened iyl benzeneboronate in a manner analogous to that described in Example 1(A) yielded (1S)-cis-5,12-diacetoxy-3-acetyl1,2,3,4,6,11 -hexahydro-6,1 1 -dioxo-1 ,3-naphthacenediyl benzeneboronate in the form of off-white crystals of melting point 191 -200 C; [α]D20 = +171.3 (c = 0.5% in dioxan).
(B) (1S)-cis-5,12-diacetoxy-3-acetyl-1,2,3,4,6,11 -hexahydro-6,11 -dioxo-1 ,3-naphthacenediyl benzeneboronate was treated with boron trichloride in a manner analogous to that described in Example 1(B) to give (1 S)-cis-3-acetyl-1,2,3,4,6,11 -hexahydro-5,12-dihydroxy-6,11 -dioxo-1 ,3-naphthacenediyl benzeneboronate in the form of orange crystals of melting point 220 -222 C; [aJ20 = + 353.3 (c = 0.1% in dioxan).
Example 5
(A) Oxidation of rac-cis-5,12-diacetoxy-3-acetoxymethyl-1,2,3,4-tetrahydro-1,3-naphthacenedlyl benzeneboronate in a manner analogous to that described in Example 1(A) gave rac-cis-5,12-diacetoxy-3- acetoxymethyl-1,2,3,4,6,11-hexahydro-6,11-dioxo-1,3-naphthacenedlyl benzeneboronate in the form of pale yellow crystals of melting point 199 -200 C.
(B) Treatment of rac-cis-5,1 2-diacetoxy-3-acetoxymethyl-1,2,3,4,6,11-hexahydro-6,11 -dioxo-1,3- naphthacenediyl benzeneboronate with boron trichloride in a manner analogous to that described in
Example 1(B) afforded rac-cis-3-acetoxymethyl-l ,2,3,4,6,11 -hexahydro-5,1 2-dihydroxy-6,11 -dioxo-1,3- naphthacenediyl benzeneboronate in the form of red crystals of melting point 200 -202 C.
Example 6
(A) Oxidation of(lS)-cis-5,1 2-diacetoxy-3-acetoxymethyl-l ,2,3,4-tetrahydro-l ,3-naphthacenediyi benzeneboronate in a manner analogous to that described in Example 1(A) gave (1 S)-cis-5,1 2-diacetoxy-3- scetoxymethyl-1,2,3,4,6,11-hexahydro-6,11-dioxo-1,3-naphthacenedlyl benzeneboronate in the form of pale yellow crystals of melting point 204 -205 C; [a]2,0 = +180.3 (c = 0.1% in dioxan).
(B) Treatment of (1S)-cis-5,12-diacetoxy-3-acetoxymethyl-1,2,3,4,6,11 -hexahyd ro-6,1 1 -dioxo-1,3naphthacenediyl benzeneboronate with boron trichloride in a manner analogous to that described in
Example 1(B) gave (1 S)-cis-3-acetoxy-methyl-1 ,2,3,4,6,1 1 -hexahydro-5,12-dihydroxy-6,11 -dioxo-1,3naphthacenediyl benzeneboronate in the form of a red semi-solid.
Example 7
(A) Oxidation of rac-cis-5,12-diacetoxy-1,2,3,4-tetrahydro-3-methyl-1,3-naphthacenediyl benzeneboronate in a manner analogous to that described in Example 1(A) gave rac-cis-5-1 2-diacetoxy-1 ,2,3,4,6,1 1 - hexahydro-3-methyl-6,11-dioxo-1,3-naphthacenediyl benzeneboronate in the form of off-white crystals of melting point 256 .259 C.
(B) Treatment of rac-cis-5,1 2-diacetoxy-1,2,3,4,6,11 -hexahydro-3-methyl-6,1 1 -dioxo-1 ,3-naphthacenediyl benzeneboronate with boron trichloride in a manner analogous to that described in Example 1(B) gave rac-cis-1 2,3,4,6,11 -hexahydro-5,1 2-dihyd roxy-3-methyl-6,1 1 -dioxo-1 ,3-naphthacene-diyl benzeneboronate in the form of red crystals of melting point 200 -217 C.
Example 8
(A) Oxidation of (1S)-cis-5,12-diacetoxy-1,2,3,4-tetrahydro-3-methyl-1,3-naphthacenediyl benzeneboronate in a manner analogous to that described in Example 1(A) gave (1S)-cis-5,12-diacetoxy-1,2,3,4,6,11- hexahydro-3-methyl-6,11-dioxo-1,3-naphthacenediyl benzeneboronate which was used in the next step without purification.
(B) Treatment of (1 S)-cls-5,1 2-diacetoxy-1 2,3,4,6,11 -hexahydro-3-methyl-6,1 1 -dioxo-1 ,3- naphthacenediyl benzeneboronate with boron trichloride in a manner analogous to that described in Example 1(B) gave (1 S)-cis-1 2,3,4,6,11 -hexahydro-5,1 2-dihydroxy-3-methyl-6,1 1 -dioxo-1 ,3-naphthacene- diyl benzeneboronate.
Claims (17)
1. Compounds of the general formula
wherein R1 represents a lower alkyl or esterified carboxy group or a group of the formula
in which R2 and R3 together form an oxo group or a protected oxo group and X represents a hydrogen atom or a hydroxy or acyloxy group, or (CH2)nOY b in which n stands for 1 or 2 and Y represents a hydrogen atom or an alkyl or acyl group, and Ar represents an aryl group.
2. Compounds of the general formula
wherein R represents a lower alkyl or esterified carboxy group or a group of the formula
in which R2 and R3 together form an oxo group or a protected oxo group and X represents a hydrogen atom or a hydroxy or acyloxy group, or
(CH2)n-OY in which n stands for 1 or 2 and Y represents a hydrogen atom or an alkyl or acyl grop, Ar represents an aryl group and R4 represents an acyl group.
3. Bac-cis-3-acetyl-1 ,2,3,4,6,1 1 -hexahydro-5, 1 2-dihydroxy-6,1 1 -dioxo-1 ,3-naphthacenediyl benzeneboronate.
4. (1 B)-cis-3-aceWl-1 ,2,3,4,6,1 1 -hexahydro-5,12-dihydroxy-6,11-dioxo-1,3-naphthacenediyl benzeneboronate.
5. (1S)-cisS-acetyl-l ,2,3,4,6,1 l-hexahydro-5,1 2-dihydroxy-6,1 l-dioxo-l ,3-naphthacenediyl benzeneboronate.
6. Rac-cis-3-acetoxymethyl-l ,2,3,4,6,11 -hexahydro-5,12-dihydroxy-6,11-dioxo-1,3-naphthacenediyl benzenboronate.
7. (1 S)-cis-3-acetoxymethyl-1 ,2,3,4,6,1 1 -hexahydro-5,12-dihydroxy-6;11 -dioxo-1 ,3-naphthacenediyl benzeneboronate.
8. Rac-cis-1,2,3,4,6,11-hexahydro-5,12-dihydroxy-3-methyl-6,11-dioxo-1,3-naphthacenediyl benzeneboronate.
9. (1 S)-cis-1,2,3,4,6,11 -hexahydro-5,12-dihydroxy-3-methyl-6,11-dioxo-1,3-naphthacenediyl benzeneboronate.
10. Rac-cis-5,12-diacetoxy-3-(1,1 -ethylenedioxyethyl)-1,2,3,4,6,11 -hexahydro-6,1 1 -dioxo-1 ,3- naphthacenediyl benzeneboronate.
11. (1R)-cis-5,12-diacetoxy-3-acetyl-1,2,3,4,6,11-hexahydro-8,11-dioxo-1,3-naphthacenediyl benzeneboronate.
12. (1 R)-cis-5,12-diacetoxy-3-(1,1 -ethylenedioxyethyl-1 ,2,3,4,6,1 1 -hexahydro-6,1 1 -dioxo-1 3- naphthacenediyl benzeneboronate.
13. (1S)-cis-5,12-diacetoxy-3-acetyl-1,2,3,4,6,11-hexahydro-8,11-dioxo-1,3-naphthacenediyl benzeneboronate.
14. Rac-cis-5,12-diacetoxy-3-acetoxymethyl-1,2,3,4,6,11 -hexahydro-6,11 -dioxo-1 ,3-naphthacenediyl benzeneboronate.
15. (1S)-cis-5,12-diacetoxy-3-acetoxymethyl-1,2,3,4,6,11-hexahydro-6,11-dioxo-1,3-naphthacenediyl benzeneboronate.
16. Rac-cis-5,12-diacetoxy-1,2,3,4,6,11 -hexahydro-3-methyl-6,1 1 -dioxo-1 ,3-naphthacenediyl benzene bomnate.
17. (1 S)-cis-5,1 2-diacetoxy-1 ,2,3,4,6,1 1 -hexahydro-3-methyl-6,11-dioxo-1,3-naphthacenediyl benzeneboronate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8312388A GB2122600B (en) | 1979-08-20 | 1983-05-05 | Hexahydronaphthacene derivatives |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7928889 | 1979-08-20 | ||
| GB8312388A GB2122600B (en) | 1979-08-20 | 1983-05-05 | Hexahydronaphthacene derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8312388D0 GB8312388D0 (en) | 1983-06-08 |
| GB2122600A true GB2122600A (en) | 1984-01-18 |
| GB2122600B GB2122600B (en) | 1984-06-13 |
Family
ID=26272626
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8312388A Expired GB2122600B (en) | 1979-08-20 | 1983-05-05 | Hexahydronaphthacene derivatives |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2122600B (en) |
-
1983
- 1983-05-05 GB GB8312388A patent/GB2122600B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB8312388D0 (en) | 1983-06-08 |
| GB2122600B (en) | 1984-06-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 732 | Registration of transactions, instruments or events in the register (sect. 32/1977) | ||
| PCNP | Patent ceased through non-payment of renewal fee |