Epoxide Cleavage Reactions of 7α, 8α- and 7β, 8β-Epoxycholestanol Acetates

Abstract

In a search for an alternative synthetic route to 32-oxygenated sterol derivatives such as 5, 7α, 8α- and 7β, 8β-epoxycholestanol acetate (9 and 10) were subjected to various conditions of epoxide cleavage. The trans-diaxial opening of the α-epoxide 9 with lithium/ethylamine gave the 7α-ol 11, whereas the 8β-ol 12 was produced from the β-epoxide 10 on reduction with lithium aluminum hydride. However, the trans-diaxial 8β-halo(or hydroxy)-7α-ols were not obtained at all on treatment of the α-epoxide 9 with various mineral acids or BF₃-etherate in benzene. Under these conditions, the C-8 carbenium ion would be the intermediate, from which the 7-ketone 13 and a mixture of Δ^{6, 8}-, Δ^{7, 9}-, Δ^{7, 14}- and/or Δ^{8, 14}-diene compounds 16, as well as Δ-<8(9)>- and Δ⁸⁽¹⁴⁾-7α-ol 14 and 4a, were produced. The latter allylic alcohol 4a, a possible synthetic precursor of 32-oxygenated sterol was prepared in 63% yield when benzene was replaced with tetrahydrofuran in the BF₃-etherate-catalyzed reaction of the α-epoxide 9.