1,2,3‐Triazoles in Peptidomimetic Chemistry

Abstract

The ability to synthesise small peptidomimetics that mimic the secondary structure of proteins is an ever expanding area of research directed at sourcing new medicinal agents and biological probes. A significant current challenge is to mimic protein epitopes under physiological conditions using small peptidomimetics that are easy to prepare. The copper‐ and ruthenium‐catalysed Huisgen cycloaddition reactions provide such a general synthetic method, with the resulting 1,2,3‐triazoles being good peptide bond mimics. The ability to prepare both 1,4‐ and 1,5‐substituted 1,2,3‐triazoles under these chemically benign conditions provides both “linear” and “bent” peptidomimetics. Examples of the use of 1,2,3‐triazoles to define the geometry and properties of a peptidomimetic abound. This review highlights such successes but also describes a number of failures in order to guide and inspire future efforts of chemists in this area.

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

“…While this ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) has as yet not found as prevalent use as the CuAAC reaction, reports of its application are increasing rapidly. Although, the RuAAC reaction has been briefly mentioned in several reviews on triazole formation [13][14][15][16][17][18][19][20][21][22][23] and metalcatalyzed reactions, [24][25][26] by now a comprehensive survey focused solely on RuAAC is needed.…”

Metal-catalyzed azide-alkyne “click” reactions: Mechanistic overview and recent trends

“…These complexes catalyzed the regioselective RuAAC reaction of terminal alkynes forming, unlike CuAAC catalysts, 1,5-disubstituted 1,2,3-triazoles, and also unlike the CuAAC catalysts, they reacted with internal alkynes providing trisubstituted 1,2,3-triazoles [28,39,40,82]. The Cp*RuCl based catalysts provided multiple application that were recently developed (vide infra) [81,[83][84][85][86][87]. M a n u s c r i p t The first mechanistic investigation was proposed by Lin, Jia, Fokin and coworkers based on DFT calculations [39].…”

“…Recent applications of Cp*RuCl-based catalysts included the synthesis of 4-haloisoxazoles and 5-halotriazoles [81], thiolactoside glycoclusters [83], one-step synthesis of triazoles [84], palladium-based metallocene complexes [85], 1,2,3-triazole peptides [86], 5-TTF-1,2,3-triazoles [87], 1,5-substitued 1,2,3-triazole amino acids [182], 5-amino-1,2,3-triazole-4-carboxylic acid [183a], and fluorinated 1,4,5-substituted 1,2,3-triazoles [183b]. RuAAC reactions catalyzed by Ru(II) complexes and RuNPs were also reported.…”

Multicomponent Click Synthesis of New 1,2,3-Triazole Derivatives of Pyrimidine Nucleobases: Promising Acidic Corrosion Inhibitors for Steel

“…Nowadays, the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC, also known as the copper(I)-catalyzed Huisgen-Meldal-Sharpless cycloaddition) is the most widely used method for the synthesis of 1,4-disubstituted 1,2,3-triazoles from a wide range of organic azides and terminal alkynes [3][4][5][6][7]. Moreover, this process allows for the assembly of complex molecules, thus generating new unknown structures with an added potential biological and engineering value [8][9][10]. Monopropargyl pyrimidine nucleobases (uracil and thymine) are versatile building blocks for the synthesis of biologically relevant 1,2,3-triazoles [11].…”