Synthesis of Glycosyl Azides and Their Applications Using CuAAC Click Chemistry to Generate Bis- and Tris(triazolyl)glycosyl Derivatives

Abstract

2,3-Unsaturated C-(triazolyl)glycosyl acetates have been synthesized from 3,4,6-tri-O-acetyl-d-glucal using C-glycosylation and click chemistry and were then used in a palladium-catalyzed Tsuji–Trost type allylic azidation reaction to afford the corresponding regioisomeric glucal-azide derivatives. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions with these glucal-based allylic azides using CuI as the catalyst, led to the corresponding glucal-based bis(triazole) derivatives. Performing further functional group modification and another click (CuAAC) reaction with each of these bis(triazolyl) glycosyl derivatives afforded tris(triazolyl)glycosyl derivatives. Two libraries of regioisomeric bis(triazole) derivatives and a small library of regioisomeric tris(triazole) derivatives of glucal were then synthesized using different alkynes.