Structural biochemistry. IV. 3β-Hydroxy-17β-(l-prolyl)amino-androst-5-ene

Abstract

The synthesis of the title compound III was studied in detail and the following combination of methods was found reliable and convenient. The oxime derivative Ib of ketone la was reduced with sodium–ethanol to 3β-hydroxy-17β-amino-androst-5-ene. The configurational assignment for amine IIa was supported by the results of a comparison with the 17α-epimer and by a proton magnetic resonance study of both isomers. Selective reaction between amine IIa and carbobenzoxy-l-proline was achieved with Woodward's reagent K. Of several procedures explored for removing the carbobenzoxy protecting group from amide IIc, palladium-catalyzed hydrogenolysis proved quite satisfactory. Hydrogenolysis of carbamate IIb to yield prolyl amide III was realized without affecting the Δ5 olefin system. A mass spectral study of amine III and the corresponding 5α-derivative IV confirmed the latter observation. A brief review of procedures for the synthesis of steroidal amines was also presented.