Efficient synthesis of novel A-ring-substituted 1,2,3-triazolylcholestane derivatives via catalytic azide-alkyne cycloaddition

A simple and convenient synthetic route is reported for the formation of novel 2 alpha-triazolylcholestane derivatives. The scheme involves transformation of the starting cholestanone to the corresponding azido compound and efficient conversions of 2 alpha-azido-5 alpha-cholestan-3-one (3) with various terminal alkynes through use of the 'click' chemistry approach. Finally, the oxo group of these heterocyclic steroidal derivatives was reduced, and the resultant mixtures of epimeric triazolyl alcohols were separated. The antiproliferative activities of the synthesized 2-triazolyl-3-ketones against three human cancer cell lines were screened. Nevertheless, only a few of the tested compounds exerted moderate cell-growth inhibition.