Green and highly efficient MCR strategy for the synthesis of pyrimidine analogs in water via C–C and C–N bond formation and docking studies

Abstract

The current study deals with the synthesis of some novel pyrimidine derivatives by the reaction of aromatic aldehydes, 2-aminobenzothiazole, and dimedone in the presence of thiamine hydrochloride (VB1) as an organocatalyst. The use of VB1 as a catalyst has eradicated the peril of metal contamination in the products that is viable for eco-friendly pathways and proven to be a better catalyst under sustainable conditions. The mechanism of the reaction involved Knoevenagel condensation followed by Michael addition. The designed protocol has many fascinating features, viz. high product yields, eco-friendly, milder reaction conditions, avoiding the use of hazardous solvent, and easily recoverable and reusable catalyst. The good functional group tolerance with a series of derivatives has been demonstrated. Molecular docking studies were performed on the synthesized compounds using Staphylococcus aureus dihydropteroate synthase (saDHPS) (6CLV) and DNA gyrase (1KZN) proteins. Furthermore, the binding mode of the ligands with the protein study was quite promising. Among the synthesized compounds, compound 5e was found to be the most potent and showed good binding interactions and the highest docking score against both proteins, 1KZN and 6CLV.