Synthesis of 2-amino-3-cyano-4H-chromen-4-ylphosphonates and their anticancer properties

Abstract

A series of 2-amino-3-cyano-4H-chromen-4-ylphosphonates have been synthesized by reacting substituted salicylaldehydes, malononitrile, and dialkylphosphites using a catalytic amount of dibutylamine as an organocatalyst employing Knoevenagel, Pinner, and phospha-Michael reactions simultaneously in ethanol. This protocol is an environmentally friendly procedure and gives high yields of the desired compounds (85-96%). In addition, no extraction or chromatography steps are needed to obtain the desired products. The compounds are tested against the viability of adenocarcinomic human alveolar basal epithelial (A549) and human epidermoid cancer (KB) cell lines using an MTT assay. Among these, diethyl 2-amino-3-cyano-4H-chromen-4-ylphosphonate and diethyl 2-amino-6-bromo-3-cyano-4H-chromen-4-ylphosphonate showed promising anticancer activity against the two tested cell lines.

Keywords: Anticancer activity; Chromenylphosphonates; Dibutylamine; Multicomponent reactions; One-pot synthesis; Organocatalyst.