Backbone rearrangements of steroidal 5-enes

Abstract

Acid-catalysed isomerisation of cholest-5-ene gives the backbone-rearranged 5,14-dimethyl-18,19-bisnor-5β,8α,9β,10α,14β-cholest-13(17)-enes with 2OR-(1) and 2OS-(2) configurations, respectively. Androst-5-ene and D-homoandrost-5-ene, in contrast, give products of only partial backbone rearrangement, with the olefinic bond at the 8,9-position; configurations at C-5, C-10, C-14, and in the D-homo-compound also at C-13, undergo equilibration to give mainly the more stable isomers with cis-fusion at the AB and CD ring juctions (Scheme 1). The symmetry characteristics of the rearranged D-homoandrost-8-enes permit racemisation, leading to total loss of optical activity after long periods of reaction. Androst-5-en-17-one rearranges in trifluoroacetic acid–dichloromethane to give 5-methyl-5β-oestr-9(11)-en-17-one (24), retaining the 14α-configuration, but methanolic sulphuric acid enforces further backbone rearrangement leading to 5-methyl-5β,14β-oestr-8-en-17-one (28) and 5-methyl-5α,10α,14β-oestr-8-en-17-one (29).

The factors influencing the stabilities of the various products are discussed, and mechanisms are proposed for the rearrangements. The ready isomerisation of D-homoandrost-5-ene shows that strain associated with the trans-fusion of rings C and D in ordinary steroids is not a requirement for backbone rearrangements to occur.