Maria José S.M. Moreno

IMPROVED SYNTHESES OF AROMATASE INHIBITORS AND NEUROACTIVE STEROIDS EFFICIENT OXIDATIONS AND REDUCTIONS AT KEY POSITIONS FOR BIOACTIVITY

An Henbest reduction, followed by the preparation of a silyl enol ether and oxidation in situ with m-CPBA has led to the neurosteroids 3α-hydroxy- and 3α,21-dihydroxy-5α-pregnanolones. Using testosterone as starting material, a new short synthesis of an aromatase inhibitor, 4-OHA, has been achieved through hydroboration/oxidation followed by a Swern type oxidation and epimerization. Another aromatase inhibitor, androst-4-ene-3,6-17-trione, has been efficiently prepared using PCC on montmorillonite K10, under ultrasonic irradiation.

A versatile and straightforward approach to the 21-oxidation of β-substituted and α,β-unsaturated 20-oxosteroids

Abstract 21-Hydroxylation and acetoxylation of 20-oxosteroids, either α,β-unsaturated or β-substituted, were successfully achieved through oxidation of the corresponding silyl enol ethers with m -CPBA followed by smooth hydrolytic cleavage of the 21-alkylsilyloxy derivatives. These conditions, which have not been previously used to synthesize such compounds, allow a high degree of regio and chemoselectivity and are specially useful for the chemical synthesis of 16α,21-dihydroxy-20-oxosteroids.