An efficient protocol for synthesis of hydroxamic acids via methane sulphonic anhydrides: An in-silico ADME properties of the synthesised amino acid derivative of hydroxamic acids

A simple, cost-effective, metal-free, and high-yielding protocol has been described for the development of hydroxamic acid scaffolds from N - α -protected amino acids and aryl carboxylic acids. This method employs economical reagents, methanesulfonic anhydride and Hunig’s base (DIPEA) and is carried out via a telescoped process. The approach offers several advantages, including the use of inexpensive reagents, high product yields, easy removal of by-products such as methanesulfonic acid, unreacted protected amino acids/aryl carboxylic acids, and DIPEA, and the ability to produce high-purity products. Moreover, the method demonstrates compatibility with various protecting groups, viz ., Boc, Fmoc, and Cbz. The efficiency of the optimized procedure was validated by applying it to a range of protected amino acids and aryl carboxylic acids, consistently delivering excellent yields and purity. Additionally, the biological potential of the synthesized hydroxamic acid derivatives was assessed through in-silico ADME profiling and molecular docking investigations accomplished against E. coli DNA Gyrase B and CYP51. This enables us to evaluate the interactions of the synthesized compounds with enzyme active sites, and the findings are discussed in detail.