Collect. Czech. Chem. Commun. 1995, 60, 257-275

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

Thi Thu Huong Nguyena, Jiří Urbanb, Eva Klinotováa, Jan Sejbala, Jiří Protivaa, Pavel Drašarc and Miroslav Protivad

a Department of Organic Chemistry, Charles University, 128 40 Prague 2, Czech Republic
b J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, 182 23 Prague 8, Czech Republic
c Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
d Post Office 31, 130 01 Prague 3, Czech Republic


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-[1H-imidazo(4,5- c)pyridin-2-yl]norcholane (IX). The structure of the products was corroborated by the mass, IR, 1H NMR and 13C NMR spectra. Some of the compounds were tested for antileukemic and for the anti-HIV activity in vitro.