RESUMO
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 mainly been prescribed as potential therapeutic agents, which interestingly represent various biological activities such as anticancer, anxiolytic, antipsychotic, anticonvulsant, antituberculosis, muscle relaxant, and antimicrobial activities. The extensive biological activities of BZDs in various fields have encouraged medicinal chemists to discover and design novel BZD-based scaffolds as potential therapeutic candidates with the favorite biological activity through an efficient protocol. Although certainly valuable and important, conventional synthetic routes to these bicyclic benzene compounds contain methodologies often requiring 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, especially 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, especially 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 by 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 design safe, environmentally benign, and economical methods for the synthesis of new and known BZDs.
Assuntos
Benzodiazepinas/síntese química , Benzodiazepinas/química , Estrutura MolecularRESUMO
Isocyanide-based consecutive Bargellini/Ugi multicomponent reactions as a combinatorial strategy have been developed for the synthesis of new class of pseudo-peptides. Via Bargellini reaction 3-carboxamido-isobutyric acids are prepared using acetone, chloroform, sodium hydroxide, and isocyanides. Then, using Ugi multicomponent reaction strategy, pseudo-peptides containing three amide bonds are synthesized using the Bargellini reaction product, aldehydes, amines, and isocyanides. This is an efficient and eco-friendly approach for easy access to wide variety of structurally diverse, drug-like pseudo-peptides from cheap and readily available precursors in high yields.
Assuntos
Amidas/química , Cianetos/química , Peptídeos/síntese química , Aldeídos/química , Aminas/química , Técnicas de Química Combinatória , Química Verde , Estrutura Molecular , Peptídeos/químicaRESUMO
Ugi four-component reactions (U-4CRs) are widely recognized as being highly efficient for the synthesis of pseudopeptides. However, the products of these reactions are not so interesting as drug candidates because they are not conformationally restricted enough for a potent interaction with biological targets. One possible way to overcome this problem is to replace amine and oxo components in the U-4CRs with cyclic imines in so-called Joullié-Ugi three-component reactions (JU-3CRs). This approach provides a robust single-step route to peptide moieties connected to N-heterocyclic motifs that are found as core skeletons in many natural products and pharmaceutical compounds. JU-3CRs also provide much better diastereoselectivity than their four-component analogues. We survey here the redesign of many synthetic routes for the efficient preparation of a wide variety of three-, five-, six-, and seven-membered heterocyclic compounds connected to the peptide backbone. Additionally, in the Ugi reactions based on the cyclic imines, α-acidic isocyanides, or azides can be replaced with normal isocyanides or acids, respectively, leading to the synthesis of N-heterocycles attached to oxazoles or tetrazoles, which are of great pharmaceutical significance. This Review includes all research articles related to Ugi reactions based on the cyclic imines to the year 2020 and will be useful to chemists in designing novel synthetic routes for the synthesis of individual and combinatorial libraries of natural products and drug-like compounds.