15-BETA-HYDROXYSTEROIDS .5. STEROIDS OF THE HUMAN PERINATAL-PERIOD - THE SYNTHESIS OF -BETA,15-BETA,17-ALPHA-TRIHYDROXY-5-PREGNEN-20-ONE FROM 15-BETA, 17-ALPHA-DIHYDROXY-4-PREGNEN-3,20-DIONE

A simple three-step synthetic method is reported on the conversion of Delta(4)-3-ketosteroids to the corresponding 3 beta-hydroxy-Delta(5)-s teroid analogues. 17 alpha-Hydroxy-4-pregnen-3,20-dione (10a) was used as a model to develop a method for the synthesis of 3 beta, 17 alpha- dihydroxy-5-pregnen-20-one (16). The major problem being the synthesis of 3,17 alpha-diacetoxy-3,5-pregnadien-20-one(14) was solved by acety lating using a mixture of acetic anhydride and perchloric acid. The co nversion of 15 beta, 17 alpha-dihydroxy-4-pregnen-3,20-dione (8), prod uct of Penicillium citrinum fermentation, to the desired 3 beta,15 bet a 17 alpha-trihydroxy-5-pregen-20-one (1), is described using a modifi cation of this method. Reaction of 8 with acetic anhydride and perchlo ric acid in ethyl acetate gave 3, 15 beta,17 alpha-triacetoxy-3,5-preg nadien-20-one (17) which on reduction with sodium borohydride gave 5-p regnen-3 beta,15 beta,17 alpha,20(S + R)-tetrols (18a and 18b); howeve r, reduction of 17 with a mixture of sodium borohydride and potassium bicarbonate gave after basic hydrolysis with methanolic sodium hydroxi de the desired product 3 beta, 15 beta,17 alpha-trihydroxy-5-pregnen-2 0-one (1) in good yield (54%).