Totally synthetic steroid heterocycles. Part 4. A stereoselective synthesis of 16-thia-D-homoestradiol 3-methyl ether and related studies

Abstract

Both a successful total synthesis of the title compound and related work are described. Two synthetic approaches have been studied utilizing the intermediate precursors, 16-thia-D-homoestra-1,3,5(10),8,14-pentaenes (1) and 9-oxo-16-thia-9,10-seco-D-homoestra-1,3,5(10),8(14)-tetraenes (15). The key steps involve double-bond reduction of these compounds. Catalytic hydrogenation and metal–ammonia reduction frequently lead to a similar unexpected ring contraction. The rearrangement, which is also examined on a bicyclic C/D model system, can be interpreted in terms of neighbouring sulphur participation. The successful route is opened up by controlled catalytic hydrogenation of the intermediates (1) and (15). Acid-catalyzed ring closure and successive reduction of the styrenoid double bond complete the stereoselective synthesis.