Efficient Synthesis of a Water-Soluble Glucoamide Inhibitor Against Human Aldose Reductase by Click Chemistry |
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| Authors: | Mikio Fujii Shinji Sudo Yasuyuki Kitagawa Keisuke Kato |
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| Institution: | 1. Faculty of Pharmaceutical Sciences , Toho University , Funabashi , Chiba , 274-8510 , Japan;2. School of Pharmacy , Showa University , Shinagawa-ku , Tokyo , 142-8555 , Japan |
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| Abstract: | 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. |
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| Keywords: | Click chemistry Aldose reductase Glycoside |
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