A novel approach to amino acid synthesis: acid-assisted reactions with dimethyl carbonate for efficient O-methylated, N,O-methylated and N-formylated derivatives

Abstract

A novel and efficient method for the modification of amino acids using a dimethyl carbonate (DMC) and acid system has been developed. N-Methylation, N,O-dimethylation, and N-formylation of various amino acids have been successfully achieved using this simple acid-assisted method (>99% conversions and >99% yields) and the modified amino acids were fully characterized using NMR spectroscopy. This method offers several advantages, including the use of a sustainable and cost-effective reagent, high selectivity, efficiency, eco-friendliness, broad applicability to a range of amino acids with different side chain functionalities, and being secure in the knowledge that there is no risk of racemization and epimerization. This study provides a new, sustainable, and practical approach for the modification of amino acids, which has potential applications in drug discovery and chemical biology.