Synthesis of deuterium-labelled 16.ALPHA.-hydroxy-4-androstene-3,17-dione and 16.ALPHA.-hydroxydehydroepiandrosterone

16α-Hydroxy-4-androstene-3, 17-dione-d5 (4) and 3β, 16α-dihydroxy-5-androsten-17-one-d6 (10) were synthesized. Treatment of 16α-bromo-5-androstene-3, 17-dione (2) with deuterium oxide and methanol-OD gave the 4-en-3-oxo derivative-d 3. The bromide 3 was converted into the 16α-hydroxide-d5 4 via controlled alkaline hydrolysis using sodium hydroxide-OD in deuterium oxide-pyridine. 3β-Hydroxy-5-androsten-17-one-d5 (8), which was obtained from 17, 17-ethylenedioxy-5-androsten-3-one (5) via treatment with potassium tert-butoxide in tert-butanol-OD, followed by lithium aluminum tri-tert-butoxydeuteride reduction and then acid hydrolysis, was derivatized to the 16α-bromide 9 by treatment with cupric bromide. The bromide 9 was similarly hydrolyzed to yield the 16α-hydroxide-d6 10.