David R. Graber

Synthesis of the four isomers of 5-hydroxy-PGI1

We wish to report here the syntheses of (5S, 6R)-5-hydroxy-, (5R, 6R)-5-hydroxy-, (5R, 6S)-5-hydroxy-, and (5S, 6S)-5-hydroxy-PGI1 and their methyl ester derivatives. Treatment of (5R, 6S)-epoxy- and (5S, 6R)-epoxy-PGF1alpha methyl esters with acid washed silica gel afforded (5R, 6R)-5-hydroxy- and (5S, 6S)-5-hydroxy-PGI1 methyl esters; correspondingly, silica promoted cyclization of (5S, 6S)-epoxy- and (5R, 6R)-epoxy-PGF1alpha methyl esters yielded (5S, 6R)-5-hydroxy- and (5R, 6S)-5-hydroxy-PGI1 methyl esters. Alternatively, the 5-hydroxyl group was introduced into the PGI1 skeleton via reaction of the 5-mercuric halides with sodium borohydride in the presence of oxygen. Stereochemical assignments were based on their mode of synthesis and 1H nmr shift differences.

Oxidative ozonolysis of 6-oxo-PGF1α, 11,15-diacetate, methyl acetal, methyl ester

Ozonolysis of 6-oxo-PGF1alpha, 11,15-diacetate, methyl acetal, methyl ester followed by oxidative workup and treatment with diazomethane gave 3-acetoxy-5-hydroxy-2-(methoxycarbonyl) cyclopentane acetic acid, gamma-lactone and dimethyl 3-acetoxy-5[[-(methoxycarbonyl)valeryl]oxy]-1,2-cyclopentane dicarboxylate as two of the major products. The mass spectral properties of the latter compound were identical with those previously published by other investigators.