Facile preparation and preliminary cytotoxicity evaluation of dehydroepiandrosterone C-16 spiro-pyrrolidine derivatives

A facile synthesis of dehydroepiandrosterones derived by C-16 spiro-pyrrolidine and their cytotoxic evaluation are reported. Seven derivatives, 3a – 3g , were prepared by the [3 + 2] cycloaddition reaction of the 16-arylidene dehydroepiandrosterone and the azomethine ylide, where the azomethine ylide was generated in situ from 11 H -indeno[1,2- b ]quinoxalin-11-one and sarcosine. Their cytotoxicity was evaluated on brine shrimp assay and the bioactivities represented by LC 50 values were found in the range of 6.19–27.2 µg/mL. Among them, the activities of 3d and 3g are the best, as manifested by LC 50 values less than 10 µg/mL. All products were confirmed by NMR, HR MS and X-ray analysis. Graphic abstract