Copper Nanoparticle‐Catalyzed Tandem Cycloaddition–Deacetylation for the Synthesis of Glycosyl Triazoles

Abstract

A practical and efficient method for the synthesis of glycosyl‐1,2,3‐triazole hybrids has been developed using copper nanoparticles supported on activated carbon as a catalyst. The methodology is based on a tandem process combining Cu‐catalyzed azide–alkyne cycloaddition with in situ deacetylation of carbohydrate derivatives under mild conditions. To the best of our knowledge, tandem CuAAC–deacetylation strategies enabling direct access to unprotected glycosyl triazoles have not been previously reported. The reaction proceeds in methanol at 65 °C using a low metal loading (1.0 mol% Cu), affording a series of glucosyl‐, galactosyl‐, and lactosyl‐triazole derivatives in good to excellent yields. The protocol was successfully performed on a larger scale (1 mmol), maintaining comparable efficiency. This approach eliminates the need for a separate deprotection step typically required for carbohydrate‐derived azides, providing a step‐economical and operationally simple route to unprotected glycosyl triazoles. A total of thirteen glycosyl‐1,2,3‐triazole derivatives were synthesized, including 12 new compounds, which were fully characterized by NMR spectroscopy and HRMS. Preliminary biological evaluation revealed promising α‐glucosidase inhibitory activity for selected disaccharide derivatives, which outperformed the reference compound. In silico ADME analysis revealed physicochemical profiles consistent with known α‐glucosidase inhibitors, supporting their suitability for localized intestinal activity.