method of biologically active prostaglandin f1: n and its johdann peasants for production.

摘要

1,198,071. Prostaglandin analogues. G. E. JUST. 5 July, 1967 [9 Aug., 1966; 24 Jan., 1967], Nos. 35550/66 and 3588/67. Heading C2C. (R 1 is H, C 1-8 alkyl, C 3-10 cycloalkyl or C 7-10 aralkyl, or phenyl optionally substituted by 1 to 3 Cl atoms or C 1-4 alkyl groups; R 2 is H or C 1-8 alkyl; R 3 and R 4 are each H or C 1-4 alkyl; and C n H 2n is C 1-8 alkylene). Compounds of the Formula VII and their salts, which are novel when they are racemates, or when they are optically active compounds excluding PGF 1 and PGF 1 # and their salts and esters, are prepared by reducing compounds of the Formula VIII e.g. with sodium borohydride, to give compounds of the Formula XIII and converting these to the required products either directly using H 2 O 2 or a percarboxylic acid and a reactant acid which is (a) an organic acid with pK less than 4; or (b) a mixture of an organic acid with pK 4 to 6 and a catalytic amount of an acid with pK less than 2; or (c) an inorganic acid with pK less than 4; or (d) a Lewis acid; or (e) mixtures of these reactant acids, or indirectly via an epoxy compound of Formula XIV using the peroxidizing compound and the reactant acid sequentially. The reduction process gives isomeric hydroxy compounds which can be separated chromatographically. The opening of the cyclopropane ring gives products having both possible configurations for the OH in the unsaturated side chain. Any acylates of the ols formed in this process may be hydrolysed conventionally. Racemates or optically active compounds can be used in the processes, and when racemates are formed these may subsequently be resolved by known methods. Esters of the acid intermediates or final products may be conventionally hydrolysed. The prostaglandin F analogues of the Formula VII, which are stated to have the pharmacological activity, especially blood pressure lowering activity, of prostaglandins F 1 and F 1 #, may be made up into pharmaceutical compositions with suitable carriers. Specifications 1,040,544 and 1,198,072 are referred to.