Practical and Selective Syntheses of S‐Acyl and N‐Acyl Glutathiones with N‐Acyl Imidazoles in Water

Abstract

AbstractA selective, mild, convenient, and green protocol for the preparation of S‐acyl and N‐acyl glutathiones is described involving the chemical modification of glutathione (GSH) with N‐acyl imidazoles at room temperature in water. The syntheses of S‐acyl glutathiones were achieved in very high yields using 1 equiv. of an N‐acyl imidazole in water at room temperature, without the need of a base. Double acylation of GSH with various N‐acyl imidazoles in weakly basic aqueous media in the presence of N‐hydroxysuccinimide (HOSu) as the activating reagent followed by selective deprotection of the S‐acyl group with aqueous ammonia at room temperature gave high yields of N‐acyl glutathiones. Moreover, the reaction could accommodate a diverse range of carboxylic acids such as (hetero)benzoic acids, phenylacetic acids, aliphatic acids from short‐chain fatty acids (including acetic acid), long‐chain polyunsaturated fatty acids, secondary or tertiary amino acids, and carboxylic acids containing clickable functional groups, fluorescent probes, or drugs.