WELPSA: A natural catalyst of alkali and alkaline earth metals for the facile synthesis of tetrahydrobenzo[b]pyrans and pyrano[2,3-d]pyrimidinones as inhibitors of SARS-CoV-2.

Since 2019, the infection of SARS-CoV-2 has been spreading worldwide and caused potentially lethal health problems. In view of this, the present study explores the most commodious and environmentally benign synthetic protocol for the synthesis of tetrahydrobenzo[b]pyran and pyrano[2,3-d]pyrimidinones as SARS-CoV-2 inhibitors via three-component cycloaddition of aromatic aldehyde, malononitrile, and dimedone/barbituric acid in water. Lemon peel from juice factory waste, namely, lemon (Citrus limon), sweet lemon (C. limetta), and Kaffir lime or Citron (C. hystrix), effectually utilized to obtain WELPSA, WESLPSA, and WEKLPSA, respectively, for the synthesis of title compounds. The catalyst was characterized by scanning electron microscope (SEM) and energy-dispersive x-ray spectroscopy (EDX). The concentration of sodium, potassium, calcium, and magnesium in the catalyst (WELPSA) was determined using atomic absorption spectrometry (AAS). The current approach manifests numerous notable advantages that include ease of preparation, handling and benignity of the catalyst, low cost, green reaction conditions, facile workup, excellent yields (93%-97%) with extreme purity, and recyclability of the catalyst. Compounds were docked on the crystal structure of SARS-CoV-2 (PDB: 6M3M). The consensus score obtained in the range 2.47-4.63 suggests that docking study was optimistic indicating the summary of all forces of interaction between ligands and the protein.