Synthesis and Biological Evaluation of 5'-Triazole Nucleosides

摘要

The 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-sialyltrans-ferase than their cytidine analogues 1a-d. 1d was the most active compound with an IC_(50) of 37.5 μM. These results suggested that the hydrophobic functionality and the cytidine group are clearly required for the improved binding.