Microwave assisted synthesis, crystal structure and modelling of cytotoxic dehydroacetic acid enamine: a natural alkaloid from Fusarium incarnatum (HKI0504)

Abstract

A novel, fast and efficient method for the synthesis of (3E)-3-(1-aminoethylidene)-6-methyl-3,4-dihydro-2H-pyran-2,4-dione, a natural antiproliferative and cytotoxic product isolated from Fusarium incarnatum (HKI0504), was developed from dehydroacetic acid and urea under solvent-free microwave irradiation. The analysis of the co-crystal structure revealed an asymmetric unit formed by a pair of molecules. Each molecule is joined by two different hydrogen bonds to another two molecules, ordered as four-unit clusters linked by π-stacking, assembled in a brick like layered structure in a set of parallel walls. Besides, the preferred tautomer for crystal structure is the enamine form. This is corroborated by computational NBO analysis, outlining the contribution of enamine resonance and modelling the non-covalent interactions involved by means of Hirshfeld surfaces and G09 counterpoise calculations.