Convenient preparative routes to 19-hydroxy, 19-oxo-, 19-oic-, and 19-nor-deoxycorticosterone

Abstract

Practical synthetic routes to 19-hydroxy-, 19-OXO-, 19-oic-, and 19-nor-deoxy-corticosterone were developed. 19-Hydroxydeoxycorticosterone (11) and its 21-acetate 10 were first prepared by two routes via O-protected 19-oxygenated intermediates 6 and 17 starting from readily available pregnenolone acetate (1) and dehydroepiandrosterone acetate (12). The key step in the first route is the application of Henbest acetoxylation at C-21 to the enamine 7 derived from 6. The second route involves introduction of a hydroxyacetyl side chain at C-17 starting with base-catalyzed condensation of 17 with methoxyacetic ester. 19-Oxo- and 19-oic-deoxycorticosterone (23 and 25) and their 21-acetates 22 and 24 were obtained via chromium trioxide oxidation of 10 under different controlled conditions. Alkaline hydrolysis of 22 under decarbonylation led to 19-nor-deoxycorticosterone(26). Alternatively, a short-step synthesis of the latter steroid from estrone methyl ether (27) was achieved by utilizing the same procedure for construction of the corticoid side chain. © 1986.