Multicomponent Reactions, Union of MCRs and Beyond

Abstract

Multicomponent reactions (MCRs), which are located between one- and two-component and polymerization reactions, provide a number of valuable conceptual and synthetic advantages over stepwise sequential approaches towards complex and valuable molecules. To address current limitations in the number of MCRs and the resulting scaffolds, the concept of union of MCRs was introduced two decades ago by Dömling and Ugi and is rapidly advancing, as is apparent by several recently published works. MCR technology is now widely recognized for its impact on drug discovery projects and is strongly endorsed by industry in addition to academia. Clearly, novel scaffolds accessible in few steps including MCRs will further enhance the field of applications. Additionally, broad expansion of MCR applications in fields such as imaging, materials science, medical devices, agriculture, or futuristic applications in stem cell therapy and theragnostics or solar energy and superconductivity are predicted.

Artificial Macrocycles by Ugi Reaction and Passerini Ring Closure

“…Maximal diversity can be reached by the concept of unions of MCR which was recently introduced (Fig. 3C) [9,37]. The convergent, economical and fast nature of MCR chemistry allows to access interesting artificial or peptidic macrocycles with a broad functional group compatibility.…”

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

“…The high combinatorial potential of Ugi-4CR together with the ability to incorporate a variety of functionalities and modifications extend its application for the generation of organic compound libraries, following hit-to-lead optimization, choosing the hit structure and final marketed drug production [54–58]. Moreover, it has been acknowledged that the combination of two privileged scaffolds in a single molecule (e.g., the combination of a peptidomimetic structure with an azole fragment [59]) potentially creates more active, new entities with unusual bioproperties [20,60–61]. In addition, the application of polyfunctional reagents in Ugi-4CR opens ways to different post-cyclization reactions, thereby broadening the scope.…”

Versatile Multicomponent Reaction Macrocycle Synthesis Using α-Isocyano-ω-carboxylic Acids

“…17 An MCR of great interest due to its bioisosteric cis-amide character is the Ugi tetrazole reaction (U-T-MCR). 18 A general, fast, and efficient synthesis οf these building blocks that does not require more than five sequential reaction steps is depicted in Scheme 3 with the used reaction conditions.…”