15-BETA-HYDROXYSTEROIDS .3. STEROIDS OF THE HUMAN PERINATAL-PERIOD - THE SYNTHESIS OF -BETA,15-BETA,17-ALPHA-TRIHYDROXY-5-PREGNEN-20-ONE - APPLICATION OF N-BUTYL BORONIC ACID PROTECTION OF A 17,20-GLYCOL

We report the synthesis of 3 beta,15 beta,17 alpha-trihydroxy-5-pregne n-20-one (1) from 3 beta,15 beta-dihydroxy-5, 16-pregnadien-20-one (11 ) in 7 steps using boronate derivatives as a means of protecting the 1 7,20-glycol side-chain of steroid intermediates. 16 alpha, 17 alpha-Ep oxy-3 beta, 15 beta-dihydroxy-5-pregnen-20-one (12), an intermediate i n the syn thesis was prepared by epoxidation of 11 using a mixture of sodium sodium hydroxide and hydrogen peroxide. Reduction of 12 with li thium aluminium hydride gave the two isomers of 5-pregnene-3 beta,15 b eta,17 alpha,20 (S+R)-tetrol (13a and 13b) which on subsequent reactio n with n-butyl boronic acid gave 5-pregnene-3 beta,15 beta,17 alpha,20 (S+R)-tetrol 17 alpha,20-butyl boronate (15a and 15b), Acetylation wit h acetic anhydride and pyridine yielded 3 beta,15 beta-diacetoxy-5-pre gnene-17 alpha,20(S+R)-diol 17 alpha,20(S+R)-butyl boronate (15c and 1 5d). Oxidative cleavage of the boronic ester using sodium hydroxide an d hydrogen peroxide gave 3 beta,15 beta-diacetoxy-5-pregnene-17 alpha, 20(S+R)-diol (13c and 13d). After isolation of these fatter two produc ts, dibromide protection of the C-5,6 olefin of 13d and oxidation with N-bromosuccinimide gave 3 beta,15 beta-diacetoxy-17 alpha-hydroxy-5-p regnen-20-one (16) which on deacetylation gave in good yield (35%) the desired product 3 beta,15 beta,17 alpha-trihdroxy-5-pregnen-20-one (1 ) in an overall yield of 24% from 11.