Reaction of 5-alkoxy-3,4-dihalo-2(5H)-furanones with secondary amines: expected versus unanticipated products and their preliminary bioactivity investigations

Abstract

Using KF as base and THF as solvent, 5-alkoxy-3,4-dihalo-2(5H)-furanones were reacted with secondary amines. The normal products, β-amino-2(5H)-furanones, were obtained via the tandem Michael addition-elimination reaction as expected in most cases. However, the reaction between diisopropylamine and 3,4-dihalo-5-methoxy-2(5H)-furanones yielded unanticipated products, methyl (E)-2-halo-4-(diisopropylamino)-4-oxobut-2-enoates. The possible synthetic mechanism involving a rearrangement reaction was proposed. The biological activity assay of products derived from the reactions of 5-alkoxy-3,4-dihalo-2(5H)-furanones with different amino compounds was preliminarily investigated by the MTT method on A549 cells in vitro, which revealed that some derivatives of amino acid esters with a benzene ring exhibited the best anticancer bioactivity.