Synthesis of New 2,5‐Dihydro‐pyrroles Through Ugi Reaction and Their Evaluations as Novel α‐Glucosidase Inhibitors

Abstract A metal‐free post‐transformation of the Ugi four‐component reaction is disclosed for the efficient construction of 2,5‐dihydropyrroles, which are important heterocyclic compounds. The synthetic process involves the Ugi‐4CR using readily available starting materials such as N ‐phenylglycine derivatives, propargylamine, and various aldehydes and isocyanides, followed by consecutive annulation under basic conditions. A new C─C bond is formed through a 5‐endo‐dig cyclization during this construction. The efficiency of this methodology is demonstrated by the rapid synthesis of ten 3‐pyrroline derivatives, exhibiting significant building‐block diversity and structural complexity, all accomplished within two operational steps. Furthermore, all synthesized compounds 6a‐j were evaluated against α‐glucosidase as an important target in the treatment of diabetes. Obtained in vitro data demonstrated that all compounds 6a‐j were more potent than standard inhibitor and the most potent compound among them was compound 6b with inhibitory activity around 3.5‐folds more than standard inhibitor.