Efficient synthesis, crystal structure, Hirshfeld surface analysis, biological evaluation, DFT calculations and Docking study of pyrano[4,3-b]pyran derivatives

Abstract

In this work we describe a simple and rapid method for the synthesis of a series of pyrano[4,3-b]pyran derivatives by a three-component reaction between 4‑hydroxy-6-methylpyran-2-one, malononitrile and a variety of aromatic and heteroaromatic aldehydes. The reactions are carried out at reflux of a water/ethanol mixture in the presence of 10 mol% of pyridinium p-toluenesulfonate as catalyst with excellent yields of expected products. The antimicrobial and anti-Alzheimer's activities of the prepared products were evaluated and some molecules gave interesting results. In addition, theoretical studies such as Density Functional Theory (DFT), IR and UV–visible spectra and molecular docking have also been carried out. Moreover, the molecular structure of one compound was confirmed by X-ray diffraction analysis with its Hirshfeld surface analysis.