The structure and function of oestrogens. V. Synthesis of (9,12,12-²H₃)- and (11ζ 12,12-²H₃)-oestradiol

Abstract

17,17-Ethylenedioxy-3-methoxy(9,12,12-²H₃)-9β-oestra-l,3,5(10)-trien-11-one (3) was reduced to the mixture of 11-epimeric alcohols (4) which upon elimination of DHO gave the (12,12-²H₂)-9(11)- dehydrooestrone derivative (5b). Treatment of (5b) with (²H₆)diborane followed by oxidation afforded the (9,12,12-²H₃)alcohol (8a); hydride reduction of the corresponding tosylate then gave 17,17-ethylenedioxy-3-methoxy(9,12,12-²H₃)oestra-l,3,5(l0)-triene (7). Acid hydrolysis of (7), followed by demethylation, and reduction with sodium borohydride yielded (9,12,12-²H₃)oestradiol (10). Sodium borohydride reduction of (11&12,12-²H₃)oestrone (6),prepared in several steps from the 9β,12,12-trideutero ketone (3), gave (11 ξ,12,12-²H₃)oestradiol (9). [The two trideuterated oestradiols (9) and (10) were required for biological studies.]