Tetrazole derivatives are a prime class of heterocycles, very important to medicinal chemistry and drug design due to not only their bioisosterism to carboxylic acid and amide moieties but also to their metabolic stability and other beneficial physicochemical properties. Although more than 20 FDA-approved drugs contain 1 H- or 2 H-tetrazole substituents, their exact binding mode, structural biology, 3D conformations, and in general their chemical behavior is not fully understood. Importantly, multicomponent reaction (MCR) chemistry offers convergent access to multiple tetrazole scaffolds providing the three important elements of novelty, diversity, and complexity, yet MCR pathways to tetrazoles are far from completely explored. Here, we review the use of multicomponent reactions for the preparation of substituted tetrazole derivatives. We highlight specific applications and general trends holding therein and discuss synthetic approaches and their value by analyzing scope and limitations, and also enlighten their receptor binding mode. Finally, we estimated the prospects of further research in this field.

Tetrazoles via Multicomponent Reactions.

The term functionalized isocyanides refers to all those isocyanides in which a neighbouring functional group can finely tune the reactivity of the isocyano group or can be exploited in post-functionalization processes. In this manuscript, we have reviewed all the isocyanides in which the pendant functional group causes either deviation from or reinforces the normal reactivity of the isocyano group and categorized them to highlight their common features and differences. An analysis of their synthetic potential and the possible unexplored directions for future research studies is also addressed.

To each his own: isonitriles for all flavors. Functionalized isocyanides as valuable tools in organic synthesis

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.

Multicomponent reactions as a potent tool for the synthesis of benzodiazepines

This paper reviews all the syntheses of 7-membered nitrogen heterocycles that are based on the Ugi multicomponent reaction Different systems may be obtained in a diversity-oriented manner employing three general strategies: i) intramolecular Ugi reaction; ii) Ugi reaction followed by cyclization involving one additional functional group; iii) Ugi reaction followed by cyclization involving two additional functional groups

Synthesis of seven-membered nitrogen heterocycles through the Ugi multicomponent reaction

Discovery of potent and selective inhibitors of the Escherichia coli M1-aminopeptidase via multicomponent solid-phase synthesis of tetrazole-peptidomimetics

Application of cyclic ketones in MCR: Ugi/amide coupling based synthesis of fused tetrazolo[1,5-a][1,4]benzodiazepines

(3+2) Annulation of amidinothioureas with binucleophile: Synthesis and antimicrobial of 3-phenylamino-5-aryl/alkyl-1,2,4-oxadiazole derivatives

Mercury(II) Chloride‐Mediated Desulphurization of Amidinothioureas: Synthesis and Antimicrobial Activity of 3‐Amino‐1,2,4‐triazole Derivatives

A Facile Diversity-Oriented Multicomponent One-Pot Synthesis of 3-Amino-6,7-dihydrobenzo[c]thiophen-4(5H)-one Derivatives from alpha-Oxo-N,S-ketene Acetal

A Facile Diversity-Oriented Multicomponent One-Pot Synthesis of 3-Amino-6,7-dihydrobenzo[c]thiophen-4(5H)-one Derivatives from α-Oxo-N,S-ketene Acetal.

Kiran M. Newase

Papers

Application of cyclic ketones in MCR: Ugi/amide coupling based synthesis of fused tetrazolo[1,5-a][1,4]benzodiazepines

(3+2) Annulation of amidinothioureas with binucleophile: Synthesis and antimicrobial of 3-phenylamino-5-aryl/alkyl-1,2,4-oxadiazole derivatives

Mercury(II) Chloride‐Mediated Desulphurization of Amidinothioureas: Synthesis and Antimicrobial Activity of 3‐Amino‐1,2,4‐triazole Derivatives

A Facile Diversity-Oriented Multicomponent One-Pot Synthesis of 3-Amino-6,7-dihydrobenzo[c]thiophen-4(5H)-one Derivatives from alpha-Oxo-N,S-ketene Acetal

A Facile Diversity-Oriented Multicomponent One-Pot Synthesis of 3-Amino-6,7-dihydrobenzo[c]thiophen-4(5H)-one Derivatives from α-Oxo-N,S-ketene Acetal.