The solvolytic ring opening of a 4β,5β-epoxy-3,6-dione steroid: preparation of potential aromatase inhibitors

Abstract

4β,5β-Epoxyandrostane-3,6,17-trione 2 undergoes cleavage of the epoxy ring as a result of nucleophilic attack by water to give both 2-hydroxy-1,4-diene-3,6-dione 3 and 7α-hydroxy-4-ene-3,6-dione 9 upon treatment with sulfuric acid in aqueous acetone. In the similar reaction in acetic acid, 2α-acetoxy-4-ene-3,6-dione 6 and its 2β-isomer 7 are produced along with the diosphenol 3. Reaction of the epoxide 2 with sodium hydroxide in methanol affords 4-methoxy-4-ene-3,6-dione 12 the dealkylation of which with hydrochloric acid yields the 4-hydroxy derivative 14.