Stereoselective routes to 14,15,17-trisubstituted-3-methoxyestra-1,3,5(10)-trienes

Abstract

An approach to the synthesis of estra-1,3,5(10),8(14)-tetraen-15-one derivatives, based upon stereoselective introduction of functionality into the 14- and 15-positions of Δ¹⁴-compounds derived from estrone, is examined. Osmium tetraoxide hydroxylation of 17,17-ethylenedioxy- or 17β-acetoxy-estra-1,3,5(10),14-tetraenes leads exclusively to 14β,15β-diols, whereas epoxidation of the 17β-acetoxy- or 17β-hydroxy-compounds gives mixtures of 14α,15α- and 14β,15β-epoxides. Treatment of these epoxides with sodium phenylselenide leads to 14α-hydroxy-15β- and 14β-hydroxy-15α-phenylselenides respectively. In the presence of aqueous perchloric acid, the 17β-acetoxy-14α,15α- and -14β,15β-epoxides are largely rearranged into 17β-acetoxy-3-methoxy-14β-estra-1,3,5(10)-trien-15-one; small amounts of trans-diols are obtained as by-products.