15β-Hydroxyesteroids (part III). Steroids of the human perinatal period: The synthesis of 3β, 15β, 17α-trihydroxy-5- pregnen-20-one. Application of n-butyl boronic acid protection of a 17,20-glycol

Article abstract of DOI:10.1016/0039-128X(95)00169-Q

We report the synthesis of 3β,15β,17α-trihydroxy-5-pregnen- 20-one (1) from 3β,15β-dihydroxy-5,16-pregnadien-20-one (11) in 7 steps using boronate derivatives as a means of protecting the 17,20-glycol side-chain of steroid intermediates. 16α,17α-Epoxy- 3β,15β-dihydroxy-5-pregnen-20-one (12), an intermediate in the synthesis was prepared by epoxidation of 11 using a mixture of sodium hydroxide and hydrogen peroxide. Reduction of 12 with lithium aluminium hydride gave the two isomers of 5-pregnene- 3β,15β, 17α,20 (S+R)-tetrol (13a and 13b) which on subsequent reaction with n-butyl boronic acid gave 5-pregnene- 3β,15β,17α,20(S+R)-tetrol 17α,20-butyl boronate (15a and 15b). Acetylation with acetic anhydride and pyridine yielded 3β,15β- diacetoxy-5-pregnene-17α,20(S+R)-diol 17α,20(S+R)-butyl boronate (15c and 15d). Oxidative cleavage of the boronic ester using sodium hydroxide and hydrogen peroxide gave 3β,15β-diacetoxy-5-pregnene- 17α,20(S+R)-diol (13c and 13d). After isolation of these latter two products, dibromide protection of the C-5,6 olfein of 13d and oxidation with N-bromosuccinimide gave 3β,15β-diacetoxy-17α- hydroxy, 5-pregnen-20-one (16) which on deacetylation gave in good yield (35%) the desired product 3β,15β, 17α-trihydroxy-5- pregnen-20-one (1) in an overall yield of 24% from 11.