15-BETA-HYDROXYSTEROIDS .6. STEROIDS OF THE HUMAN PERINATAL-PERIOD - THE PREPARATION AND REACTIONS OF 3-BETA-HYDROXY-5,15-ANDROSTADIEN-17-ONE - THE SYNTHESIS OF 3-BETA,15-BETA-DIHYDROXY-5-ANDROSTEN-17-ONE AND DERIVATIVES

A successful approach to the synthesis of 3 beta,15 beta-dihydroxy-5-a ndrosten-17-one (14d) has been developed using trichloroethoxy ethers as intermediates in the synthesis of the corresponding alcohols. 3 bet a-Methoxymethoxy-5,15-androstadien-17-one (10c) was prepared by a sele nation/dehydroselanation strategy from 3 beta-methoxymethoxy-5-androst en-17-one (14c). Base-catalyzed reaction of trichloroethanol with 10c gave 3 beta-methoxymethoxy-15 beta-trichloroethoxy-5-androsten-17-one (14g). Under the same conditions, 3 beta-acetoxy-5,15-androstadien-17- one (10b) gave 3 beta-hydroxy-15 beta-trichloroethoxy-5-androsten-17-o ne (14f) which was characterized after conversion to 14g. Cleavage of the trichloroethoxy group in 14f with zinc or zinc/copper couple gave 14g. The acid-catalyzed hydrolysis of 17,17-ethylenedioxy-5,15-androst adien-3 beta-ol (15) gave 3 beta-hydroxy-5-15-androstadien-17-one (10a ) as the major product along with 14d. However, addition of water to 1 0a in the presence of acid gave the desired product 14d in poor yield (15%).