Stereoselective synthesis of some methyl-substituted steroid hormones and their in vitro cytotoxic activity against human gastric cancer cell line MGC-803

Abstract

A series of 3-, 7-, 15-, and 16-methyl-substituted steroid analogs were synthesized via a highly stereoselective 1,6-conjugate addition. Under the catalysis of CuBr, AlMe(3) reacted with four steroid dienone precursors to afford either the corresponding alpha-epimer of C-3 and C-7 methyl-substituted steroids as the major products, and the ratio of alpha/beta was up to 10/1. No beta-epimer has been detected for methyl addition at C-16. However, under the same reaction conditions, enantioselective methyl addition at C-15 afforded the 15beta-epimer as the major product. The preliminary SAR analysis showed that the methyl substituents at C-7alpha and C-15beta positions lead to a dramatical increase in potency against human gastric cancer cell line MGC-803. Copyright 2010 Elsevier Inc. All rights reserved.