Multicomponent Reactions in the Synthesis of Pharmacologically Active Molecules

Abstract

Multicomponent reactions (MCRs) have emerged as a transformative approach in modern synthetic organic chemistry, offering highly efficient, atom-economical, and environmentally sustainable pathways for the synthesis of pharmacologically active molecules. These one-pot processes enable the rapid construction of complex molecular architectures by combining three or more starting materials into a single product, significantly reducing reaction steps, waste generation, and purification requirements. Classical MCRs such as the Strecker, Biginelli, and Hantzsch reactions, along with isonitrile-based reactions like the Ugi and Passerini reactions, have been extensively utilized to generate diverse heterocyclic scaffolds with broad therapeutic applications.  Recent advancements in MCR strategies, including post-condensation cyclization, diversity-oriented synthesis (DOS), and asymmetric multicomponent reactions (AMCRs), have further expanded their applicability in drug discovery. Moreover, the integration of green chemistry principles, innovative catalytic systems, and modern technologies such as flow chemistry and artificial intelligence has enhanced the efficiency and sustainability of these processes. MCR-derived compounds have demonstrated significant potential across multiple therapeutic areas, including central nervous system disorders, antimicrobial, antiviral, and cardiovascular diseases. Overall, MCRs represent a powerful platform for accelerating pharmaceutical innovation while aligning with the principles of sustainable chemistry.