Patent GB-1505442-A (GB)
Title: Prostaglandins
IPC: C07C405/00
Filed: 1976-07-08
Abstract: 1505442 4,5,6 - Trinor - 3,7 - inter - mphenylene - prostaglandins UPJOHN CO 8 July 1976 [13 Aug 1975 (2) 1 June 1976] 28440/76 Heading C2C [Also in Division C3] The invention comprises optically active 4,5,6 - trinor - 3,7 - inter - m - phenylene - prostaglandins of the Formulµ I, II and III or racemates thereof, wherein Q is wherein R 3  is H or C 1-4  alkyl and R 1  is H, C 1-12  alkyl, C 3-10  cycloalkyl, C 7-12  aralkyl or phenyl optionally substituted by 1 to 3 halogen atoms or C 1-4  alkyl radicals, and the pharmacologically acceptable salts thereof when R 2  is H, and their preparation by standard methods. The following intermediates are also prepared: 2-(m-bromomethylbenzyl) malonic acid and its dimethyl and diethyl esters; 3-(mbromomethylphenyl)propionic acid and its methyl ester; dimethyl 2-(m-acetoxymethylbenzyl) malonate; 3 - (m - hydroxymethylphenyl) propionic acid and its methyl ester; methyl 3 - (m - formylphenyl) propionate; dl- 6 - endo - (1 - heptenyl) - 2 - exo - {m - [2 - (methoxycarbonyl)ethyl]} - benzylbicyclo[3,1,0]hexan - 3 - one; dl - 6 - endo - (1,2 - dihydroxyheptyl) - 2 - exo - {m - [2 - (methoxycarbonyl)- ethyl]}benzylbicyclo[3,1,0]hexen- 3 - one and its bis-mesylate; methyl 9-oxo-11α,15α-bis-(trifluoroacetoxy) - 4,5,6 - trinor - 3,7 - inter - mphenylene - prost - trans - 13 - enoate; dl - 8- {m - [2 - (methoxycarbonyl)ethyl]phenyl} - 7- oxatricyclo[4,2,0,0<SP>2,4</SP>] - octane - 6 - endo - carboxaldehyde 2,2 - dimethyltrimethylene acetal; dl - 2 - exo - {m - [2 - (methoxycarbonyl)- methyl]benzyl} - 3 - exo - hydroxybicyclo- [3,1,0]hexone - 6 - endo - carboxaldehyde 2,2- dimethyltrimethylene acetal; dl-2-exo-{m-[2- (methoxycarbonyl)ethyl]benzyl} - 3 - exo - pivaloyloxybicyclo[3,1,0]hexane - 6 - endo - carboxaldehyde and its 2,2-dimethyltrimethylene acetal; dl - 2 - exo - {m - [2 - (methoxycarbonyl)- ethyl]benzyl} - 3 - exo - pivaloyloxy - 6 - endo- [cis - 1 - heptenyl (and 1,2 - dihydroxyheptyl)]- bicyclo[3,1,0]hexane; dl 2 - exo - [m - (2 - carboxyethyl)benzyl (and m - (2 - methoxycarbonylethyl)benzyl] - 3 - exo - hydroxy - 6- endo - (cis - 1 - heptenyl)bicyclo[3,1,0]hexane; dl - 2 - exo - {m - [2 - (methoxycarbonyl)ethyl]- benzyl} - 6 - endo - (cis - 1 - heptenyl - and 1,2- dihydroxyheptyl) - bicyclo[3,1,0]hexan - 3 - one; 5α - hydroxy - 3α - (2 - tetrahydropyranyloxy)- 2# - [3(s) - (2 - tetrahydropyranyloxy - trans- 1 - octenyl] - 1α - cyclopentaneacetic acid; 2- methylene - 4α - (2 - tetrahydropyranyloxy) - 3# - [3(s) - (2 - tetrahydropyranyloxy) - trans - 1- octenyl] - cyclopentanol; 2 - methylene - 4α- (2 - tetrahydropyranyloxy) - 3α - [3(s) - (2- tetrahydropyranyloxy)- trans - 1 - octenyl]- cyclopentanone; 2α - [m - (3 - hydroxypropyl)- benzyl] - 4α - (2 - tetrahydropyranyloxy) - 3#- [3(s) - (2 - tetrahydropyranyloxy) - trans - 1- octenyl]cyclopentanol; 4,5,6 - trinor - 3,7- inter - m - phenylene - PGE, 11,15 - bis - tetrahydropyranyl ether and its methyl ester; 2α- (2 - hydroxyethyl) - 4α - (2 - tetrahydropyranyloxy) - 3# - [3 - (2 - tetrahydropyranyloxy)- trans - 1 - acetyl] - 1α - cyclopentanol, and its diacetate; 5α - acetoxy - 3α - (2 - tetrahydropyranyloxy - 2# - [3 - (2 - tetrahydropyanyloxy)- trans - 1 - octenyl] " 1α - cyclopentane ethanol; 5α - acetoxy - 3α - (2 - tetrahydropyranyloxy)- 2# - [3 - (2 - tetrahydropyranyloxy) - trans - 1- octenyl] - 1α - cyclopentaneacetic acid; 1α- acetoxy - 2 - methylene - 4α - (2 - tetrahydropyranyloxy) - 3# - [3 - (2 - tetrahydropyranyloxy) - trans - 1 - octenyl]cyclopentane; 2α- (2 - acetoxyethyl) - 4α - (2 - tetrahydropyranyloxy) - 3# - [3 - (2 - tetrahydropyranyloxy)- trans - 1 - octenyl] - 1α - cyclopentanol and its pivalate; 5α - pivaloyloxy - 3α - (2 - tetrahydropyranyloxy) - 2# - [3 - (2 - tetrahydropyranyloxy) - trans - 1 - octenyl] - 1α - cyclopentaneethanol; 5α - pivaoloyloxy - 3α - (2 - tetrahydropyranyloxy) - 2# - [3 - (2 - tetrahydropyranyloxy) - trans - 1 - octenyl] - lx - cyclopentaneacetic acid; and 2 - methylene - 1α - pivaloyloxy - 4α - (2 - tetrahydropyranyloxy) - 3# - [3- (2 - tetrahydropyranyloxy) - trans - 1 - octenyl]- cyclopentane. Pharmaceutical compositions, suitable for oral, parenteral, rectal, vaginal and topical administration, contain the above prostaglandins together with pharmaceutically acceptable carriers. The compounds possess similar pharmacological properties to those of the naturally occurring prostaglandins.