Vilsmeier reagent initialed sequential one-pot multicomponent synthesis of N,O-disubstituted glycolamides as dipeptidyl peptidase 4 inhibitors

Abstract

A series of N,O-disubstituted glycolamide derivatives have been successfully synthesized through Vilsmeier reagent initialed sequential one-pot multicomponent procedure from α-chloro N-arylacetamides with formamide/PBr3 and acid chloride. The three-step synthesis involved Vilsmeier formyloxylation reaction, decarbonylation, and esterification. The strategy was also applicable to α-chloro N-(naphthalenyl)acetamide to prepare the corresponding N,O-disubstituted glycolamide products. All of N,O-disubstituted glycolamides were evaluated against dipeptidyl peptidase 4 inhibitory activity. Based on the inhibitory results, several of O-furan-2-carbonyl and O-quinoline-8-sulfonyl N-aryl glycolamide compounds possessed the better effective inhibition of dipeptidyl peptidase 4.