Synthesis and biological evaluation of 5′-triazole nucleosides

The first series of 5'-triazole cytidines 1a-d and adenosines 2a-c was prepared and evaluated for inhibitory potency toward alpha-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 alpha-2,3-sialyltransferase than their cytidine analogues 1a-d. 1d was the most active compound with an IC50 of 37.5 mu M. These results suggested that the hydrophobic functionality and the cytidine group are clearly required for the improved binding.