Synthesis and Molecular Docking Studies of 3-Methyl-1,4-diarylazetidin-2-ones

Abstract

The trans isomers of 3-methyl-1,4-diarylazetidine-2-ones were isolated from the reactions of N,1-diarylmethanimine with the ketene generated from propionyl chloride via [2+2] cycloaddition protocol. The reaction was optimised by varying different parameters such as temperature, solvent and bases. The trans β-lactams were obtained as the major diastereomers and the structure was confirmed from the coupling constants of the respective hydrogens from the ¹H NMR spectra. The structures of the β-lactams were elucidated by ¹H and ¹³C NMR spectral techniques and ESI-MS spectroscopy. The synthesized compounds were evaluated for the binding affinities. To gain insights to mechanism of action, the interactions between the synthesized compounds and the selected microbial target S. aureus DNA Gyrase B protein were examined. These investigations shed light on the potential binding modes of (±) trans 3-methyl-1,4-diarylazetidine-2-ones, enhancing our understanding of the mechanism of action.