Ionic Liquid Mediated Ugi/SN2 Cyclization: Synthesis of 1,2,3-Triazole Containing Novel 2,5-Diketopiperazines

Abstract

The Ugi four-component reaction is versatile multicomponent reaction for generation of complex diversity, herein, we developed a novel methodology by using 4-((1-((tetrahydrofuran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde as one of the components in Ugi 4CR that contains 1,2,3-triazole moiety which is a privileged molecule in medicinal chemistry to obtain Ugi adducts under room temperature ionic liquids as medium of solvent, then followed SN2 pathway cyclization to get triazole containing 2,5-diketopiperazine derivatives in good yield using basic ionic liquids as a catalyst.

Synthesis of Peptidomimetics via IMCR/Post-Transformation Strategy

“…Particularly, the isocyanide-based multicomponent reactions (IMCRs), such as Ugi and Passerini reactions, are the most relevant for constructing peptidomimetics since they give access to linear peptides and depsipeptide-like structures. The post I-MCR-transformation strategy, via the Ugi-4CR followed by ciclization, is the most efficient alternative to produce cyclic peptidomimetics like DKPs [3]. The synthesis of 2,5-DKPs through post-I-MCRs-transformation strategy required additional processes like deprotection and activation-based cyclization under harsh acidic and/or basic conditions, using non-eco-friendly solvents [4][5][6][7].…”