Enzymatic Synthesis of Indole-Based Imidazopyridine using α-Amylase

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 alpha-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 alpha-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. A biocatalytic process for synthesizing clinically important indole-based imidazo[1,2-a]pyridine derivatives using the alpha-amylase catalyzed Groebke-Blackburn-Bienayme (GBB) multicomponent reaction of 2-aminopyridine, indole-3-carboxaldehyde, and isocyanide has been developed. Further, alpha-amylase from Aspergillus oryzae was immobilized onto magnetic metal-organic framework (MOF) materials [Fe3O4@MIL-100(Fe)] to make it a robust and reusable catalyst for this transformation. image