Diastereoselective Synthesis of Novel Spiro-Phosphacoumarins and Evaluation of Their Anti-Cancer Activity

Abstract

Herein we present the regio- and diastereoselective synthesis of novel pyrrolidine-fused spiro-dihydrophosphacoumarins via intermolecular [3 + 2] cycloaddition reaction. The presented approach is complementary to existing ones and provides an easy entry to the otherwise inaccessible derivatives. Additionally, the unprecedented pathway of the reaction of 4-hydroxycoumarin with azomethine ylides is described. The anti-cancer activity of the obtained compounds was tested in vitro, the most potent compound being 2.6-fold more active against the HuTu 80 cell line than the reference 5-fluorouracil, with a selectivity index > 32.

Frontiers in New Drug Discovery: From Molecular Targets to Preclinical Trials

“…The tested drugs were internalized in cancer cells and were able to activate the apoptotic pathway [1]. The regio-and diastereoselective synthesis of novel pyrrolidine-fused spiro-dihydrophosphacoumarins were presented in [2]. This new approach in the synethesis of spiro-dihydrophosphacoumarins is complementary to existing approaches and provides an easy entry to the otherwise inaccessible derivatives, some of which have significantly greater cytotoxic activity against the HuTu 80 cell line than the reference 5-fluorouracil.…”