Synthesis of Nα-Protected Diazomethylketone Using COMU and Its Application in the Preparation of Bromomethylketones and Selenazoles: Study of Antibacterial and Antioxidant Activities

Abstract

An efficient protocol for the synthesis of N-protected diazomethylketone was developed using (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)-dimethylamino-morpholinomethylene) methanaminium hexa-fluorophosphate (COMU) and N-nitrosourea (NNU) is developed.  Conversion of carboxylic acids to diazomethylketones in an excellent yield was obtained under milder reaction conditions, through a simple workup. Further, the synthesized compounds were used for the preparation of bromomethylketones using 45% aqueous HBr and selenazoles. Prepared bromomethylketones were subjected for their antibacterial activity against Escherichia coli and Staphylococcus aureus strains and antioxidant studies. Antibacterial activity reveals that the compound Fmoc-Phe-CO-CH₂-Br exhibited the zone of inhibition with respect to Streptomycin sulphate standard. For antioxidant assay, % RSC of Fmoc-Ala-CO-CH-N₂, Fmoc-Phe-CO-CH₂-Br and Fmoc-Phe-CO-CH-N₂ exhibited free radical inhibition or scavenger activity with 2, 2-diphenyl-1-picrylhydrazyl (DPPH). The synthesized compounds were characterized by HRMS, ¹H NMR, and ¹³C NMR studies.