Synthesis of 19-hydroxy-1β,19-cyclosteroids

Abstract

19(R/S)-Substituted 1β,19-cyclo-5α-steroids have been synthesized by reductive cyclization of 3,17-dioxo-5α-androst-1-en-19-al with zinc in aqueous acetic acid or lithium in ammonia. The major product from the zinc reaction, the 19(R)-cyclopropanol, exists in equilibrium with the 3-hemiketal; the minor product, the 19(S)-alcohol, is isolated as the silyl ether and deprotected to give the 19(S)-cyclopropanol. The major product from the lithium–ammonia reaction is the 19(S)-cyclopropanol. Neither acid nor base treatment of the 19(R)- and 19(S)-alcohols gives evidence of their interconversion. Structures are established by NMR measurements.