Biocatalytic tandem multicomponent reactions for one-pot synthesis of 2-Amino-4H-Pyran library and in vitro biological evaluation

Abstract

A simple, effective and ecofriendly biocatalytic method has been developed to construct 2-amino-4H-pyrans via tandem multi-component reaction (MCR) of aldehyde, malononitrile and ethyl acetoacetate in one pot. The catalytic activity of lipases in different reaction media and other experimental conditions were investigated. The reported methodology offers a mild approach to obtain a library of 2-amino-4H-pyrans with good yields and favorable function group tolerance. Moreover, molecular docking experiments have been carried out to investigate the possible mechanism of this enzyme-initiated one-pot reaction. In addition, eight compounds in the library have been chosen in order to evaluate the in vitro antitumor activities against three cell lines (A549, Hela and HepG2). The results illustrated that 4v had the most potent antitumor activity, whose IC50 is 0.0517 μM in A549 cells.