Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors, 1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol: Syntheses and glycosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol
Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors, 1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol: Syntheses and glycosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-D-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannitol
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DOI：
10.1016/s0008-6215(97)00099-2
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发表时间：
1997-06-20
影响因子：
3.1
通讯作者：
Wrodnigg, T
中科院分区：
文献类型：
--
作者：
Andersen, SM;Ebner, M;Wrodnigg, T
1，2，5-三脱氧-2-氟-1，5-亚氨基-D-葡萄糖醇，1-脱氧野尻霉素的2-脱氧氟衍生物，以及1，2，5-三脱氧-1-氟-2，5-亚氨基-D-甘露糖醇和2，5-二脱氧-2，5-亚氨基-1-O-甲基-D-甘露糖醇，两种天然产物和强效葡萄糖苷酶抑制剂2，5-二脱氧-2，5-亚氨基-D-甘露糖醇的新类似物，的合成，其特征在于葡萄糖异构酶催化的醛糖-酮糖互变反应作为合成的关键步骤。用这些化合物和先前获得的1-脱氧野尻霉素的脱氧氟衍生物，采用来自各种来源的葡糖苷酶进行的抑制研究的结果表明，氟取代羟基官能团引起抑制效力的损害。这种效应对于C-6位的羟基最小，对于C-2和C-3位的取代最多大四个数量级。(C)1997 Elsevier Science Ltd.
1,2,5-Trideoxy-2-fluoro-1,5-imino-D-glucitol, the 2-deoxyfluoro derivative of 1-deoxynojirimycin, as well as 1,2,5-trideoxy-1-fluoro-2,5-imino-D-mannit and 2,5-dideoxy-2,5-imino-1-O-methyl-D-mannitol, two new analogues of the natural product and powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol, were synthesised featuring glucose isomerase-catalysed aldose-ketose interconversion reactions as the key steps of the syntheses. Results of inhibition studies conducted with these compounds and previously obtained deoxyfluoro derivatives of 1-deoxynojirimycin, employing glucosidases from various sources, showed that the replacement of a hydroxyl function by fluorine caused an impairment of the inhibitory potency. This effect was smallest for the hydroxyl group at C-6 and up to four orders of magnitude larger for replacements at C-2 and C-3. (C) 1997 Elsevier Science Ltd.