Patent GB-1424806-A (GB)
Title: Cyclopentane derivatives
IPC: C07D309/12
Filed: 1972-02-18
Abstract: 1424806 Prostaglandins; phosphonate and phosphonium intermediates MAY & BAKER Ltd 15 Feb 1973 [18 Feb 1972] 7640/72 Headings C2C and C2P The invention comprises prostaglandins of the formula wherein R<SP>1</SP> is H of C 1-12  alkyl; R<SP>2</SP> and R<SP>3</SP> each are H or C 1-4  alkyl; R<SP>4</SP> is H or C 1-10  alkyl; n is 4 or 6; and the symbols A, B, X and Y have any one of the following combinations: (a) A is >CH 2 , B is >CHOH, X is -CH 2 CH 2 -, and Y is >CHOH; (b) A is >C=O; B is >CH 2 ; X is -CH 2 CH 2 - or trans-CH = CH-, and Y is >CHOH or >C=O; or (c) A is >CHOH, B is >CH 2 , X is -CH 2 CH 2 - or trans-CH = CH-, and Y is >CHOH; and when R<SP>1</SP> is H, non-toxic salts thereof, and their preparation. The processes comprising: (i) for those compounds of Formula I above in which A and Y are identical, each being either >C=O or >CHOH, the acid hydrolysis of compounds of the Formula V wherein A and Y are both >C=O or >CHOH and R<SP>8</SP> is an optionally substituted 2-tetrahydropyranyl radical; (ii) for those compounds of Formula I above in which B is >CH 2 , A is >C=O and Y is >CHOH, the acid hydrolysis of compounds of the Formula VI wherein the symbols R<SP>9</SP> are identical alkyl radicals or together form an ethylene linkage optionally substituted by identical alkyl radicals on each carbon atom; (iii) of those compounds of Formula I above in which A is >CH 2 , B and Y are >CHOH and X is -CH 2 CH 2 -, the acid hydrolysis of compounds of the Formula VII (iv) for those compounds of Formula I above in which B is >CH 2 , X is -CH 2 CH 2 - or trans- CH=CH- and A and Y are >CHOH, the reduction of compounds of Formula I above in which X is -CH 2 CH 2 - or trans-CH = CH-, A is >C = O, Y is >C = O or >CHOH, and B is >CH 2 , with carbonyl reducing agents; (v) for those compounds in which B is >CH 2 , Y is -CH 2 CH 2 -, A is >C=O and Y is >C=O or >CHOH, the hydrogenation of the corresponding compounds of Formula I in which X is trans-CH=CH-, A is > C = O and Y is >C=O or >CHOH; (vi) for those compounds of Formula I above in which B is >CH 2 , X is -CH 2 CH 2 - and A and Y are >CHOH, the reduction of compounds of Formula I above in which B is >CH 2 , except for those compounds in which X and A is -CH 2 CH 2 - and >CHOH respectively. The acids then obtained may be esterified or converted into salts and any resulting esters hydrolysed. The following intermediates are also obtained : 2 - (3-acetoxyoctyl)-3-cyano-5 - hydroxycyclopentanone, 3,4 - dihydroxy - 2 - (3 - hydroxyoctyl)cyolopentanecarbonitrile, 3,4 - bis - (2- tetrahydropyranyloxy) - 2 - [3 - (2 - tetrahydropyranyloxy)octyl]cyclopentanecarbonitrile, 3,4- bis - (2 - tetrahydropyranyloxy) - 2 - [3 - (2- tetrahydropyranyloxy)octyl]- cyclopentanecarbaldehyde, ethyl 7-{ 3,4-bis-(2-tetrahydropyranyloxy) - 2 - [3 - (2 - tetrahydropyranyloxy)- octyl]cyclopentyl}heptatrans - 2, trans - 4, trans - 6 - trienoate, ethyl 7 - {3,4 - bis - (2- tetrahydropyranyloxy) - 2 - [3 - (2 - tetrahydropyranyloxy ) octyl ] cyclopentyl} heptanoate, 2 - (7- acetoxyheptyl) - 3 - cyano - 5- hydroxycyclopentanone 2 - (7 - acetoxyheptyl- 3 - cyano - 5 - (2 - tetrahydropyranyloxy)- cyclopentanone, 3 - hydroxy - 2 - (7 - hydroxyheptyl) - 4 - (2 - tetrahydropyranyloxy)cyclopentanecarbaldehyde, 2 - (7 - hydroxyheptyl)- 3 - [3 - oxo - trans - 1 - octenyl (or decenyl, or heptenyl)] - 5 - (2 - tetrahydropyranloxy)- cyclopentanol, compounds of Formula V above, and 2-(7-hydroxyheptyl)-3-(4-methyl-3- oxooct - trans - 1 - enyl) - 5 - (2 - tetrahydropyranyloxy)cyclopentanol. (5 - Ethoxycarbonylpenta - trans - 2, trans - 4- di - enyl)triphenylphosphonium bromide is obtained by reacting triphenylphosphine with ethyl 6-bromo-hexa-traps-2, trans-4-dienoate. Hexanoylmethylene triphenylphosphorane is prepared by reacting sodium carbonate with (2 - oxoheptyl)triphenylphosphonium chloride resulting from the reacting between 1-chloroheptan-2-one and triphenylphosphine. Pentanolymethyl triphenylphosphorane, octanoylmethylene triphenylphosphorane, (2 - oxohexyl) triphenylphosphonium chloride and (2-oxononyl) triphenylphosphonium chloride are obtained in a similar manner. Dimethyl (3 - methyl - 2 - oxoheptyl)phosplaonate is obtained by reacting dimethyl methylphosphonate with butyl lithium and ethyl 2- methylhexanoate. Pharmaceutical compositions, suitable for oral, parenteral, rectal or vaginal administration, contain the above prostaglandins or non-toxic salts thereof together with pharmaceutical carriers or coatings. The compounds produce hypotension and brochodilation, inhibit gastric acid secretion and stimulate uterine contraction.