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-5alpha-androstan-17beta-ol acetate is described. Cyclization of 1,4-dibromo-1,4-seco-2,3bisnor-5alpha-androstan-17beta-ol acetate with benzylamine in the presence of potassium iodide 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 first hormonally active steroid containing nitrogen as a heteroatom in the perhydrocyclopentanophenanthrene nucleus.

Decarboxylative Halogenation of Organic Compounds

“…The double iododecarboxylation of 1,8-naphthalenedicarboxylic acid proceeds smoothly without the formation of an anhydride (see compound 232). Remarkably, the iododecarboxylation of electron-rich aromatic acids could be achieved employing LiI instead of I 2 , in trifluoroethanol or hexafluoroisopropanol as the solvent (230,85). 182 Although the reaction is not selective, and excessive ring halogenation is observed, quenching the reaction in the early stages allows the isolation of the iododecarboxylation products in useful yields.…”