A Pregnane Steroid As The Chiral Auxiliary In 1,3-Dipolar Azomethine Ylide'S Cycloaddition: Asymmetric Synthesis And Anticancer Activity Of Novel Hybrid Compounds

Hybrid chiral molecules containing frameworks of a pregnane steroid and 5-arylpyrrolidine-2,4-dicarboxylate have been synthesized for the first time in a diastereomerically pure form. Chiral pregnane-based acrylate induced stereoselective formation of all-cistrisubstituted pyrrolidine moiety under cycloaddition with stabilized N-metalated azomethine ylides. beta-Dipeptidic fragment was built up at C-3 pregnane position using consequent acryloylation and stereoselective cycloaddition with stabilized N-metalated azomethine ylide. All novel hybrid molecules demonstrated micromolar cytotoxic activity against human cervical epithelioid cancer HeLa cell culture in native and estradiol-stimulated forms and breast carcinoma MCF-7 cell culture. The most of hybrid compounds are less toxic towards human skin fibroblasts HSF as compared with studied hormonal tumor cells.