Patent GB-1420338-A (GB)
Title: 8,12-di-isoprostanoic acid derivatives
IPC: C07C401/00
Filed: 1972-12-12
Abstract: 1420338 Prostaglandins CARLO ERBA SpA 12 Dec 1972 [17 Dec 1971] 57333/72 Heading C2C The invention comprises prostaglandins of the Formulae I and II wherein R<SP>1</SP> is H or C 1-12  alkyl; one of R<SP>2</SP> and R<SP>3</SP> is H and the other is OH or R<SP>2</SP> and R<SP>3</SP> together form an oxo group; the symbol = is a single or cis-double bond; R<SP>4</SP> is -CH 2 CH 2 -, -OCH 2 -, trans -CH=CH-, or -SCH 2 -; n is 3 or 4; each of R<SP>5</SP> and R<SP>6</SP> is H or C 1-4  alkyl, one of R' and R<SP>8</SP> is H and the other is OH; and double bond a is a trans-double bond, with the proviso that when R<SP>4</SP> is trans -CH = CH the symbol = is a cis-double bond, and pharmaceutical acceptable salts thereof when R<SP>1</SP> is H and their preparation. The compounds are prepared by reacting lactols of the Formula III wherein one of R<SP>7</SP> and R<SP>8</SP> is OH or an etherified group and the other is H, and Y is OH or an etherified hydroxy group with Wittig reagents comprising the group CH 2 CH 2 R<SP>4</SP>COOR<SP>1</SP> to give compounds of the Formula IV optionally hydrogenating the 5(6) double bond and if necessary, deetherifying compounds of Formula IV or their hydrogenation products, or (a) oxidizing the 9-hydroxy group of compounds of Formula IV wherein Y is an etherified hydroxy group and one of R<SP>7</SP> I  and R<SP>8</SP> I  is an etherified hydroxy group and the other is H or the 5(6) hydrogenation products to give compounds of the Formula V which may either be deetherified, or its 9-oxo group reduced to give the corresponding 9α- and 9#-hydroxy compounds and the mixture, in any order, separated and deetherified; or (b) reacting compounds of Formula IV in which Y is etherified hydroxy and one of R<SP>7</SP> I  and R<SP>8</SP> I  is etherified hydroxy and the other is H, or 5(6) hydrogenated products thereof with compounds of the formula R<SP>9</SP>SO 2 X, wherein R<SP>9</SP> is optionally substituted alkyl or aryl and X is halogen to give compounds of the Formula VIII which are then reacted with carboxylic acid salts to yield a mixture of compounds of Formulae IV and V which mixtures are then, in any order, hydrolysed, deetherified and separated. dP-5-Benzyloxy 1-(or -4-methoxybenzyloxy)- methyl-4-hydroxy-2-cyclopentene-1-acetic acid is resolved via its dehydroabietylamine salt. The following intermediates are also prepared: 5α-methoxymethyl (or benzyloxymethyl- or p-methoxybenzyloxymethyl-)-2#,4#-dihydroxy- 3α-iodo-1#-cyclopentane acetic acid γ-lactone and its 4#-acetate, 5α-methoxy methyl-2#,4#- dihydroxy-1#-cyclopentane acetic acid γ-lactone and its 4#-acetate, 4#-p-toluenesulphonate, 4#- methanesulphonate and 4#-benzenesulphonate, 5α-methoxymethyl 2#-hydroxy-3-cyclopentene- 1#-acetic acid γ-lactone, 5α-hydroxymethyl- 2#,4α-dihydroxy-1#-cyclopentane acetic acid γ- lactone 4α-p-phenylbenzoate, 5α-formyl-2#4,α- dihydroxy-1#-cyclopentane acetic acid γ-lactone 4α-p-phenylbenzoate and 4α-acetate, 5α-(3-oxo- 2-R 6 -4-R 5 -oct (or non)-trans-1-enyl)-2#,4α-dihydroxy-1#-cyclopentane acetic acid γ lactone 4α-p-phenylbenzoate and 4α-acetate 5α-(3-hydroxy-2-R 6 -4-R 5 -oct (or non)-trans-1-enyl)-2#, 4α-dihydroxy-1#-cyclo pentane acetic acid γ- lactone and its 4α-p-phenylbenzoate and 4α- acetate, compounds of the Formula XXI 5α - p - methoxybenzyloxymethyl - 2#,4# - dihydroxy-1#-cyclopentane acetic acid γ-lactone and its 4#-acetate, 4#-p-toluenesulphonate, 4#- methane-sulphonate and 4#-benzenesulphonate, 5α-benzyloxy (or p-methoxybenzyloxy or methoxy) methyl-2#-4α-dihydroxy-1#-cyclopentaneacetic acid γ-lactone and its 4α-propionate, 4α-formate and its 4α-p-phenylbenzoate. Pharmaceutical compositions, suitable for oral, parenteral or rectal administration, contain the above prostaglandins or salts thereof and pharmaceutical acceptable diluents or carriers. The compounds possess activities similar to those of the naturally occurring prostaglandins.