Synthetic steroids. Part III. The preparation of 3β,15β,17β-trihydroxyandrost-5-ene and the attempted preparation of 3β,15α,17β-trihydroxyandrost-5-ene

Abstract

3β-Acetoxyandrost-5-en-17-one has been converted into 3β-acetoxy-16α-bromo-17-ethylenedioxyandrost-5-ene which was subsequently hydrolysed and dehydrobrominated to give 3β-hydroxyandrosta-5,15-dien-17-one. 1,4-Addition of benzyl alcohol to this conjugated ketone gave 3β-acetoxy-15β-benzyloxyandrost-5-en-17-one from which the benzyloxy-group could be removed with calcium in liquid ammonia to give 3β,15β,17β-trihydroxyandrost-5-ene.

Protection of the 5,6-double bond in 3β-acetoxyandrosta-5,15-dien-17-one was achieved by its selective reaction with sulphuryl chloride–pyridine to give the 5α,6β-dichloro-derivative. Acid-catalysed migration of the remaining double bond Δ¹⁵ to Δ¹⁴ was then followed by hydration of the 14,15-double bond with diborane. The stereospecificity of reagent attack at the steroid α-face previously observed with the reaction of diborane at the Δ¹⁴-position was not observed and a 1 : 1 mixture of 3β,15β,17β-trihydroxy-14β-androst-5-ene and 3β,15α,17β-trihydroxyandrost-5-ene was obtained after removal of the 5,6-protecting groups.