Synthesis of 16α-Hydroxyandrost-4-ene-3, 17, 19-trione and 3β, 16α-Dihydroxyandrost-5-ene-17, 19-dione : Potential Intermediates of Estriol Biosynthesis

Abstract

16α-Hydroxyandrost-4-ene-3, 17, 19-trione (10) was synthesized from the 16α-hydroxy-6β, 19-epoxy-17-one 3 via protection of the 16α-hydroxy function as its tert-butyldimethylsilyl ether or acetate. Reductive cleavage of the epoxy ring of the silyl ether 4 or the acetate 5 with zinc dust gave the 19-alcohol 6 or 7, which was treated with pyridinium dichromate or Jones reagent, respectively, and then hydrolyzed with diluted sulfuric acid, yielding the desired steroid 10. 3β, 16α-Dihydroxyandrost-5-ene-17, 19-dione (14) was also synthesized from 5α-bromo-3β, 16α-diacetoxy-6β, 19-epoxyandrostan-17-one (11) through the intermediates 12 and 13 with the 3β- and 16α-hydroxy functions protected as their acetates in a reaction sequence similar to that above.