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[摘要]：5a-Carba-alpha-D-glucopyranosylamine validamine, and analogous compounds valienamine and valiolamine, have proved to be important lead compounds for development of clinically useful medicines, including the very strong glucosidase inhibitor, voglibose, N-(1,3-dihydroxyprop-2-yl)valiolamine, now used widely as a clinically important antidiabetic agent. In this review, we describe recent advances in development of glycosidase inhibitors on the basis of the ground-state mimics of the postulated glycopyranosyl cation, considered to be formed during hydrolysis of glycopyranosides, and introduce a new type of highly potent alpha-fucosidase inhibitor, 5a-carba-alpha-L-fucopyranosylamine, alpha-fuco validamine. Interestingly, the corresponding beta-anomer, and in particular its D-enantiomer, has been shown to possess very strong cross-inhibitory activity toward beta-galactosidase and beta-glucosidase. Structure and inhibitory activity relationships concerning these, alpha,beta-fuco derivatives, as well as parent, alpha,beta-galacto validamines are discussed here with reference to our results. |
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