1-N-Iminosugars: Potent and Selective Inhibitors of -Glycosidases
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- 作者：Yoshitaka Ichikawa ; Yasuhiro Igarashi ; Mie Ichikawa ; and Yoshitomo Suhara
- 刊名：Journal of the American Chemical Society
- 出版年：1998
- 出版时间：April 8, 1998
- 年：1998
- 卷：120
- 期：13
- 页码：3007 - 3018
- 全文大小：336K
- 年卷期：v.120,no.13(April 8, 1998)
- ISSN：1520-5126
文摘
A series of 1-N-iminosugars were synthesized to supplythe need for glycosidase inhibitors that areboth highly potent and selective for 
-glycosidases. Designed onthe basis of the transition-state model of the-glucosidase reaction, these iminosugar inhibitors differ from thecurrently available inhibitors in possessinga nitrogen atom at the anomeric position of the pyranose ring, therebygenerating a positive charge on theanomeric position rather than on the ring oxygen of the sugar.Their syntheses, starting with a readily availablecarbohydrate derivative, involve (i) introduction of an aminofunctionality as an azido group, (ii) formation ofa 1-N-iminopyranose ring with reductive amination, and (iii)stereoselective introduction of a hydroxymethylor methyl group and were accomplished in a highly stereoselective andefficient manner. The inhibitorypotencies of the 1-N-iminosugars were evaluated againstseveral 
- and -glycosidases, and they were foundto be extremely potent and highly specific against the corresponding-glycosidases, with Ki values inthenanomolar range.
-glycosidases. Designed onthe basis of the transition-state model of the-glucosidase reaction, these iminosugar inhibitors differ from thecurrently available inhibitors in possessinga nitrogen atom at the anomeric position of the pyranose ring, therebygenerating a positive charge on theanomeric position rather than on the ring oxygen of the sugar.Their syntheses, starting with a readily availablecarbohydrate derivative, involve (i) introduction of an aminofunctionality as an azido group, (ii) formation ofa 1-N-iminopyranose ring with reductive amination, and (iii)stereoselective introduction of a hydroxymethylor methyl group and were accomplished in a highly stereoselective andefficient manner. The inhibitorypotencies of the 1-N-iminosugars were evaluated againstseveral - and -glycosidases, and they were foundto be extremely potent and highly specific against the corresponding-glycosidases, with Ki values inthenanomolar range.