Multicomponent reactions as a potent tool for the synthesis of benzodiazepines

Benzodiazepines (BZDs), a diverse class of benzofused seven-membered N-heterocycles, display essential pharmacological properties and play vital roles in some biochemical processes. They have majorly been prescribed as potential therapeutic agents, which interestingly represented various biological activities such as anticancer, anxiolytic, antipsychotics, anticonvulsant, antituberculosis, muscle relaxant, and antimicrobial. The extensively biological activities of BZDs in various fields have encouraged medicinal chemists to discover and design novel BZDs-based scaffolds as potential therapeutic candidates with the favorite biological manner through an efficient protocol. Although certainly valuable and important, conventional synthetic routes of these bicyclic benzene compounds contain methodologies often required multistep procedures, which suffer from waste materials generation and lack of sustainability. By contrast, multicomponent reactions (MCRs) have recently advanced as a green synthetic strategy for synthesizing BZDs with the desired scope. In this regard, MCRs specially Ugi and Ugi-type reactions, efficiently and conveniently supply various complex synthons, which can easily be converted to the BZDs via suitable post-transformations. Also, MCRs specially Mannich-type reactions, provide speedy and economic approaches for the one-pot and one-step synthesis of BZDs. As a result, various functionalized-BZDs have been achieved via developing mild, efficient, and high-yielding MCR protocols. This review covers all aspects of the synthesis of BZDs with a particular focus on the MCRs as well as the mechanism chemistry of synthetic protocols. The present manuscript opens a new avenue for organic, medicinal, and industrial chemists to designing safe, environmentally benign, and economical methods for the synthesis of new and known BZDs.