Synthesis and Biological Evaluation of 5′‐Triazole Nucleosides

Abstract

AbstractThe first series of 5′‐triazole cytidines 1a‐d and adenosines 2a‐c was prepared and evaluated for inhibitory potency toward α‐2,3‐sialyltransferase. The synthesis of target compounds was achieved by converting the 5′‐alcohol of protected nucleosides to the azide derivatives, which were then coupled with the alkynes by copper(I)‐catalyzed cycloaddition to give protected 5′‐triazole nucleosides 3a‐d/7a‐c, followed by deprotection. 5′‐Triazole adenosines 2a‐c were less efficient inhibitors of α‐2,3‐sialyltransferase than their cytidine analogues 1a‐d. 1d was the most active compound with an IC50 of 37.5 μM. These results suggested that the hydrophobic functionality and the cytidine group are clearly required for the improved binding.