Synthesis of Several Hydroxylated 23-(Benzimidazol-2-yl-, Benzoxazol-2-yl and Benzothiazol-2-yl)norcholanes and Some Related Compounds

The bile acids Ia - Id (lithocholic, chenodeoxycholic, deoxycholic, cholic) and their derivatives ( O -acetylated acids and O -acetylated acid chlorides) reacted under various conditions with 1,2-diaminobenzene, 2-aminophenol and 2-aminothiophenol and afforded the title benzimidazoles II and VII , benzoxazoles V and benzothiazoles VI . Alkylation of the benzimidazole derivative IIa with 2-dimethylaminoethyl chloride resulted in 3α-hydroxy-23-[1-(2-dimethylaminoethyl)ben zimidazol-2-yl]- norcholane ( IVa ). The use of 1,2-diamino-4-methylbenzene enabled the preparation of 3α-acetoxy-23-[5(6)-methylbenzimidazol-2-y l]norcholane ( VIII ). Reactions of the 3α-hydroxy compounds IVa , Va and VIa with succinic anhydride resulted in the hemisuccinates IVi - VIi . The boric acid mediated condensation of O -acetyllithocholic acid ( Ie ) with 3,4-diaminopyridine gave compound X which was transformed to 3α-acetoxy-23-[1 H -imidazo(4,5- c )pyridin-2-yl]norcholane ( IX ). The structure of the products was corroborated by the mass, IR, 1 H NMR and 13 C NMR spectra. Some of the compounds were tested for antileukemic and for the anti-HIV activity in vitro.