Enzyme-Catalysed Multicomponent Reactions (MCRs) for the Green Synthesis of Bioactive Heterocycles-A Review

The increasing need for sustainable and eco-friendly chemical processes has driven considerable interest in biocatalysis and multicomponent reactions (MCRs) as greener approaches in organic synthesis. Enzymes, owing to their remarkable selectivity, catalytic efficiency, and ability to function under mild conditions, have emerged as powerful biocatalysts for promoting one-pot multicomponent transformations. These enzyme-catalysed MCRs associate well with the principles of green chemistry by minimalizing waste, reducing solvent usage, shortening reaction times, and avoiding hazardous reagents. Moreover, the phenomenon of enzyme promiscuity—where enzymes catalyse non-natural reactions—has expanded their applicability to a wide range of synthetic transformations. This article provides a complete overview of MCRs employed in the construction of an extensive variety of heterocyclic scaffolds—including pyridines, pyrimidines, pyrazoles, phthalazines, benzoxazines, triazoles, oxadiazoles, xanthenes, furans, indoles, imidazole’s, quinolines, and benzothiazole derivatives—catalysed by biological catalysts such as enzymes. This review highlights recent advances in enzyme-catalysed multicomponent and domino reactions, with particular emphasis on their reaction scope and advantages over traditional chemical methods, focusing on developments reported between 2020 and 2025. The integration of enzyme catalysis with multicomponent strategies represents a promising frontier in sustainable chemistry, offering new avenues for the eco-friendly synthesis of complex and biologically active molecules.