Bromodimethylsulfonium bromide: A novel reagent for the one-pot synthesis of potent Na-ureido peptides and study of molecular docking and antibacterial activities

Abstract

Na-protected ureidopeptides were efficiently synthesized using bromodimethylsulfonium bromide mediated Curtius rearrangement through the in-situ generation of carboxylated sulfonium intermediate. Conversion of carboxylic acids to ureidopeptides in good yield was achieved in one pot under mild reaction conditions through a simple workup. To check the binding modes and binding affinity of urea functional group with target protein, the synthesized compounds were subjected to docking studies. Docking scores confirmed that the Boc-Leu-ψ [NHCONH]-Ala-OMe and Leu-ψ [NHCONH]-Ala-OMe molecules had the lowest energy and good agreement with the results of antibacterial studies against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeroginosa in comparison with streptomycin sulphate as a standard. The synthesized compounds were well characterized by IR, 1H NMR, 13C NMR, and mass spectral studies.