Patent GB-1432950-A (GB)
Title: Cyclopentane aldehydes as chemical intermediates
IPC: C07C47/36
Filed: 1973-01-15
Abstract: 1432950 Aldehydes and enones and their uses as intermediates in the preparation of prostaglandin or like compounds IMPERIAL CHEMICAL INDUSTRIES Ltd 18 Oct 1973 [10 Nov 1972 15 Jan 1973 15 Aug 1973] 52010/72 2033/73 39578/73 Heading C2C The invention relates to aldehydes of the general formula in which R<SP>1</SP> is a carboxy or hydroxymethyl radical or an alkoxycarbonyl radical of up to 11 carbon atoms, A is an ethylene or cisvinylene radical, and R<SP>2</SP> and R<SP>3</SP> which may be the same or different, are hydroxy radicals or protected hydroxy radicals, or R<SP>1</SP> and R<SP>2</SP> together form an oxycarbonyl radical, in which an oxygen atom is bonded to carbon atom 9 and the carbon atom is bonded to carbon atom 2, and bearing 0 to 1 alkyl substituent of 1 to 4 carbon atoms on carbon atom 2, 3 or 4, provided that when R<SP>1</SP> is a methoxycarbonyl radical, and either R<SP>2</SP> is an acetoxy radical and R<SP>3</SP> is a tetrahydropyran-2-yloxy radical, or R<SP>2</SP> is a 4-phenylbenzoyloxy radical and R<SP>3</SP> is an acetoxy radical, A is a cis-vinylene radical are prepared by the acid hydrolysis of an acetal of a formula in which X represents 2 alkoxy radicals each of up to 5 carbon atoms or an alkylene dioxy radical of 2 to 6 carbon atoms. The compounds claimed per se are methyl 7-(2 beta-formyl-3 alpha, 5 alpha - di(4 - phenylbenzoyloxy)- cyclopent - 1 alpha - yl]hept - 5 - cis - enoate, methyl 7 - [2 beta - formyl - 3 alpha,5 alphadyhydroxycyclopent-1 alpha - yl]hept - 5 - cisenoate, methyl 7 - [2 beta - formyl - 3 alphahydroxy - 5 alpha - (4 - phenylbenzoyloxy)- cyclopent - 1 alpha - yl]heptanoate, methyl 7 - [2 beta - formyl 3 alpha - hydroxy - 5 alpha - (4 - phenylbenzoyloxy)cyclopent - 1 alpha - yl]hept - 5 - cis - enoate or 7 - [3 alpha- 3,5 - dinitrobenzoyloxy) - 2 beta - formyl - 5 alpha - hydroxycyclopent - 1 alpha - yl]hept- 5-cis-enoic acid lactone. The aldehydes may be used to prepare prostaglandin or prostaglandinlike compounds of the general formula in which R<SP>4</SP> is a hydroxy radical or an alkanoyloxy radical of 1 to 4 carbon atoms and R<SP>5</SP> is a hydrogen atom, Y is an ethylene or transvinylene radical, Z is an ethylene or cis-vinylene radical, and R<SP>6</SP> is: a branched or unbranched alkyl radical of 4 to 10 carbon atoms; a radical of the formula -A<SP>1</SP>.OR<SP>7</SP>, wherein A<SP>1</SP> is an alkylene radical of 1 to 9 carbon atoms and R<SP>7</SP> is an alkyl radical of 1 to 9 carbon atoms or a cycloalkyl radical of 5 to 7 carbon atoms, provided that A<SP>1</SP> and R<SP>7</SP> together contain not more than 10 carbon atoms; a radical of the formula -A<SP>2</SP>R<SP>8</SP>, wherein A<SP>2</SP> is a direct bond or an alkylene radical of 1 to 3 carbon atoms, and R<SP>8</SP> is an aryl radical which is unsubstituted or which is substituted by halogen atoms, nitro radicals, alkyl, halogenalkyl, alkoxy or alkoxyalkyl radicals each of 1 to 3 carbon atoms or dialkylamino radicals wherein each alkyl is of 1 to 3 carbon atoms; a radical of the formula -A<SP>3</SP>.A<SP>4</SP>.R<SP>9</SP>, wherein A<SP>3</SP> is an alkylene radical of 1 to 3 carbon atoms bearing as substituents 0, 1 or 2 alkyl radicals each of 1 to 3 carbon atoms, A<SP>4</SP> is an oxygen or sulphur atom, a sulphinyl radical or an alkylimino radical of up to 4 carbon atoms, and R<SP>9</SP> is an aryl, benzyl or furfuryl radical optionally substituted by hydroxy, nitro or phenyl radicals, halogen atoms, alkyl, alkenyl, halogenalkyl, alkoxy, alkenyloxy, or acylamino radicals of 1 to 4 carbon atoms or dialkylamino wherein each alkyl is of 1 to 3 carbon atoms; or a radical of the formula -A<SP>3</SP>.A<SP>5</SP>.R<SP>10</SP>, wherein A<SP>3</SP> has the meaning stated above, A<SP>5</SP> is an oxygen or sulphur atom, a sulphinyl, sulphonyl, imino or alkylimino radical of up to 4 carbon atoms or a direct bond, or A<SP>3</SP> and A<SP>5</SP> are each a direct bond, and R<SP>10</SP> is an aromatic heterocyclic radical of one or two 5- or 6-membered rings, containing in one ring only, 1 or 2 non-adjacent nitrogen hetero-atoms, and optionally bearing 1 to 3 alkyl radicals or halogen atoms as substituents; which compound contains 0 or 1 alkyl radicals of 1 to 4 carbon atoms as substituents in the trimethylene group; and for those compounds wherein R<SP>1</SP> is a carboxyl radical, the pharmaceutically acceptable salts thereof, by reacting a compound of the Formula I with a phosphonate of the formula in the presence of a strong base, or with a phosphorane of the formula wherein R<SP>11</SP> is an alkyl radical of 1 to 4 carbon atoms, to give an enone which is reduced to a prostaglandin or prostaglandin-like compound. The invention also relates to an enone of the general formula in which R<SP>6</SP>, Z, R<SP>1</SP>, R<SP>2</SP> and R<SP>3</SP> are as above and which contains 0 or 1 alkyl radicals of 1 to 4 carbon atoms as substituents in the trimethylene group which may be prepared by reacting the aldehyde compound with a phosphonate of the formula (R<SP>11</SP>O) 2 PO.CH 2 COR<SP>6</SP> or a phosphorane of the formula Ph 3 P : CH.COR<SP>6</SP> in the presence of a strong base. Enones claimed per se are methyl 15-oxo-9 alpha, 11 alpha-di(4-phenylbenzoyloxy) - 5 - cis, 13 - trans - prostadienoate, methyl - 15 - oxo - 9 alpha, 11 alpha - di(4- phenylbenzoyloxy) - 16 - (3 - trifluoromethylphenoxy) - 17,18,19,20 - tetranor - 5 - cis, 13 - trans - prostadienoate, methyl 9 alpha, 11 alpha - dihydroxy - 15 - oxo - 5 - cis, 13- trans - prostadienoate, methyl 15 - (4 - methoxymethylphenyl) - 15 - oxo - 9 alpha, 11 alpha - di - (4 - phenylbenzoyloxy) - 16,17,- 18,19,20 - pentanor - 5 - cis.13 - trans - prostadienoate, methyl 11 alpha - hydroxy - 16- (indol - 5 - yloxy) - 15 - oxo - 9 alpha - (4- phenylbenzoyloxy) - 17,18,19,20 - tetranor- 13 - trans - prostanoate, 11 alpha - (3,5 - dinitrobenzoyloxy) - 9 alpha - hydroxy - 15- oxo - 16 - (3 - trifluoromethylphenoxy) - 17, 18,- 19, 20 - tetranor - 5 - cis,13 - trans - prostadienoic acid 1,9 alpha-lactone and methyl 11 alphahydroxy - 15 - oxo - 9 alpha - (4 - phenylbenzoyloxy) - 5 - cis, 13 - trans - prostadienoate. Many examples are given together with the preparation of starting materials and intermediates.