Neighboring group participation ☆: Part 15. Stereoselective synthesis of some steroidal tetrahydrooxazin-2-ones, as novel presumed inhibitors of human 5α-reductase

Abstract During the alkaline methanolysis of 3β-acetoxy-21-chloromethyl-pregn-5-ene-20β- N -phenylurethane, and its p -substituted phenyl derivatives, cyclization occurs, in the course of which 17β-[3-( N -phenyl)tetrahydrooxazin-2-on-6-yl]androst-5-en-3β-ol and its p -substituted phenyl derivatives are formed. The cyclization takes place with (N − -6) neighboring group participation. Oppenauer oxidation of the 3β-hydroxy- exo -heterocyclic steroids yielded the corresponding Δ 4 -3-ketosteroids. The structures of the new compounds were proved by IR, 1 H and 13 C NMR spectroscopy, using up-to-date measuring techniques such as 2D-COSY, HMQC, and HMBC. The inhibitory effects (CI 50 ) of the Δ 4 -3-ketosteroids on 5α-reductase were studied.