PMDTA-catalyzed multicomponent synthesis and biological activity of 2-amino-4H-chromenes containing a phosphonate or phosphine oxide moiety

Abstract

A new approach for the preparation of (2-amino-3-cyano-4H-chromen-4-yl)phosphonate derivatives is described. The multicomponent reaction of salicylaldehydes, malononitrile and dialkyl phosphites catalyzed by pentamethyldiethylenetriamine (PMDTA) provided the bicyclic derivatives in high yields. The method developed did not require chromatographic separation, since the products could be recovered from the reaction mixture by simple filtration. Our approach made also possible condensation with secondary phosphine oxides, and this reaction has not been previously reported in the literature. The crystal structures of five derivatives were studied by single-crystal XRD analysis. The in vitro cytotoxicity on different cell lines and the antibacterial activity of the (2-amino-4H-chromen-4-yl)phosphonates synthesized were also explored. According to the IC₅₀ values determined, several derivatives showed moderate or promising activity against mouse fibroblast (NIH/3T3) and human promyelocytic leukemia (HL-60) cells. Furthermore, three (2-amino-3-cyano-4H-chromen-4-yl)phosphine oxides were active against selected Gram-positive bacteria.