Efficient Synthesis of a Water-Soluble Glucoamide Inhibitor Against Human Aldose Reductase by Click Chemistry

摘要

While D-glucose is the natural substrate of aldose reductase (AR) in the polyol pathway, the K_m value of D-glucose against AR is large. A glucoamide 1 was designed as a tool to investigate whether AR has a strong affinity for the open form of D-glucose. Glucoamide 1 was synthesized in high yield by modification of the reaction condition for click chemistry. It was found that our modified condition was applicable for highly polar alkynes and gave coupling products in excellent yield (90% to 100%). Although weak inhibitory activity against AR was observed, kinetic studies showed that AR does not accept glucoamide 1 in its active site.