Apparent bioisosteric replacement of -S- by NCN: synthesis of N-cyano-2-aza-A-nor-5.alpha.-androstan-17.beta.-ol acetate, an aza steroid androgen

Abstract

The synthesis of N-cyano-2-aza-A-nor-5.alpha.-androstan-17.beta.-ol acetate is described. Cyclization of 1,4-dibromo-1,4-seco-2,3-bisnor-5.alpha.-androstan-17.beta.-ol acetate with benzylamine in the presence of KI gives the N-benzyl-2-aza-A-nor steroid. Debenzylation with cyanogen bromide (Von Braun reaction) affords the N-cyano-2-aza-A-nor steroid, which has androgenic activity slightly weaker than that of the corresponding thia compound. The results indicate that NCN may be substituted for -S- as well as for =S. This compound is the 1st hormonally active steroid [in rats] containing nitrogen as a heteroatom in the perhydrocyclopentanophenanthrene nucleus.