Enzymatic Synthesis of Indole‐Based Imidazopyridine using α‐Amylase

Abstract

The imidazo[1,2‐a]pyridine scaffold has gained significant attention due to its presence as a lead structure in several commercially available pharmaceuticals like zolimidine, zolpidem, olprinone, soraprazan, etc. Further, indole‐based imidazo[1,2‐a]pyridine derivatives have been found interesting due to their anticancer and antibacterial activities. However, limited methods have been reported for the synthesis of indole‐based imidazo[1,2‐a]pyridines. In this study, we have successfully developed a biocatalytic process for synthesizing indole‐based imidazo[1,2‐a]pyridine derivatives using the α‐amylase enzyme catalyzed Groebke‐Blackburn‐Bienayme (GBB) multicomponent reaction of 2‐aminopyridine, indole‐3‐carboxaldehyde, and isocyanide. The generality and robustness of this protocol were shown by synthesizing differently substituted indole‐based imidazo[1,2‐a]pyridines in good isolated yields. Furthermore, to make α‐amylase a reusable catalyst for GBB multicomponent reaction, it was immobilized onto magnetic metal‐organic framework (MOF) materials [Fe3O4@MIL‐100(Fe)] and found reusable up to four consecutive catalytic cycles without the significant loss in catalytic activity.