Patent GB-1330003-A (GB)
Title: Cyclopentane derivatives
IPC: C07C61/06
Filed: 1970-05-27
Abstract: 1330003 Cyclopentane derivatives MAY & BAKER Ltd 26 May 1971 [27 May 1970] 25486/70 Headings C2C and C2P The invention comprises novel cyclopentane derivatives of the formula wherein A is >C=O or -CH(OR<SP>3</SP>), R<SP>1</SP> is C 1-10  alkyl, C 3-10  cycloalkyl or C 3-10  cycloalkyl- C 1-4  alkyl, m is 4 or 6, R<SP>2</SP> is OH or OR<SP>4</SP>, N(R<SP>5</SP>)R<SP>6</SP> or, except when A is >C=O, NHN(R<SP>5</SP>)R<SP>6</SP>, wherein R<SP>4</SP> is C 1-4  alkyl, R<SP>5</SP>, R<SP>6</SP>, R<SP>7</SP> and R<SP>8</SP> each are H or C 1-4  alkyl, and R<SP>3</SP> is H, C 1-4  alkyl, or, when R<SP>2</SP> is OH or OR<SP>4</SP>, a group -COR<SP>9</SP>, wherein R<SP>9</SP> is C 1-4  alkyl, and when A is -CH(OR<SP>3</SP>)- the symbols R<SP>3</SP> both are H or identical groups and, when R<SP>2</SP> is OH, non-toxic salts thereof. The compounds of the above formula may be prepared by one of the following methods:- (a) Compounds wherein R<SP>2</SP> is OH and R<SP>3</SP> is H or alkyl by the alkaline hydrolysis of the corresponding compounds in which R<SP>2</SP> is OR<SP>4</SP>. (b) Compounds wherein A is CH(OR<SP>3</SP>), R<SP>2</SP> is OR<SP>4</SP>, and R<SP>3</SP> is H by the acid hydrolysis of the corresponding di-tetrahydropyranyl ethers, or by the reduction of the double bonds in compounds of the formula wherein n is 1 or 2. (c) Compounds wherein A is >C=O, R<SP>2</SP> is OH and R<SP>3</SP> is H by the acid hydrolysis of compounds of the formula wherein the symbols R<SP>12</SP> are identical C 1-4  alkyl or together form an ethylene linkage unsubstituted or substituted by identical alkyl groups on each C atom. (d) The amides, hydrazides, esters and ethers are made by usual methods from the appropriate acids, esters, acid halides and free hydroxy containing compounds. Ethyl 7 - { 3 - (2 - tetrahydropyranyloxy) - 2- [3 - (2 - tetrahydropyranyloxy)octyl]cyclopentyl}- heptanoate (A) is obtained by the following reaction sequence. 1,4-Dioxa-6-(2-cyanoethyl)- spiro[4,4] - nonane -# 1,4 - dioxa - 6 - (3- oxooctyl)spiro[4,4]- nonane -# 1,4 - dioxa - 6- (3 - hydroxyoctyl)spiro[4,4]nonane -# 1,4-dioxo - 6 - (3 - acetoxyoctyl)spiro[4,4]nonane -# 2- (3 - acetoxyoctyl)cyclopentanone -# 1 - acetoxy- 2 - (3 - acetoxyoctyl) - cyclopent - 1 - ene -# 2- (3 - acetoxyoctyl)cyclopent - 2 - enone -# 2 - (3- acetoxyoctyl) - 3 - cyanocyclopentanone -# 3- hydroxy - 2 - (3 - hydroxyoctyl)cyclopentane carbonitrile -# 3 - (2 - tetrahydropyranyloxy) - 2- [3 - (2 - tetrahydropyranyloxy)octyl]cyclopantane carbonitrile -# 3 - (2 - tetrahydropyranyloxy) - 2- [3 - (2 - tetrahydropyranyloxy)octyl]cyclopentane carbaldehyde -# ethyl 7 - {3 - (2 - tetrahydropyranyloxy) - 2 - [3 - (2 - tetrahydropyranyloxy)- octyl]cyclopentyl}hepta - 2,4,6 - trienoate -# A. Ethyl 7 - [3 - hydroxy - 2 - (3 - hydroxyoctyl)- cyclopentyl]hepta - 2,4,6 - trienoate is obtained by adding 5 - ethoxycarbonylpenta - 2,4 - dienyltriphenylphosphorane to 3-hydroxy-2-(3- hydroxyoctyl)cyclopentane carbaldehyde, resulting from the treatment of 2-(3-acetoxyoctyl)-3- cyanocyclopentanone with a solution of di-isobutylaluminium hydride in benzene. 1,4 - Dioxa - 7 - (6 - carboxyhexyl) - 6 - (3- hydroxyoctyl)spiro[4,4]nonane is made by hydrolysing 1,4 - dioxa - 7 - (6 - ethoxycarbonylhexyl)- 6 - (3 - hydroxyoctyl)spiro[4,4]nonane, obtained by adding 4-ethoxycarbonylpenta-2,4-dienyltriphenylphosphorane to 1,4-dioxa-7-formyl-6- (3 - hydroxyoctyl)spiro[4,4]nonane resulting from the action of di-isobutylaluminium hydride on 1,4 - dioxa - 6 - (3 - acetoxyoctyl) - 7 - cyanospiro- [4,4]nonane, which is made by reaction of ethylene glycol on 2-(3-acetoxyoctyl)-3-cyanocyclopentanone. 5 - Ethoxycarbonylpenta - 2,4 - dienyltriphenylphosphorane is obtained by adding aqueous sodium hydroxide to 5-ethoxycarbonyl-2,4-dienyltriphenylphosphonium bromide, resulting from the reaction between triphenylphosphine and ethyl 6-bromohexa-2,4-dienoate. Pharmaceutical compositions, suitable for oral, parenteral or rectal administration, contain the above novel compounds or salts thereof in association with pharmaceutical carriers or coatings. The compounds possess hypotensive activity and reduce gastric acid secretion.