Cystic fibrosis and diabetes: isoLAB and isoDAB, enantiomeric carbon-branched pyrrolidine iminosugars
Cystic fibrosis and diabetes: isoLAB and isoDAB, enantiomeric carbon-branched pyrrolidine iminosugars
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DOI：
10.1016/j.tetlet.2010.05.131
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发表时间：
2010-08-11
影响因子：
1.8
通讯作者：
Fleet, George W. J.
中科院分区：
文献类型：
--
作者：
Best, Daniel;Jenkinson, Sarah F.;Fleet, George W. J.
丙酮化物是从D-核糖合成isoDAB和从D-塔格糖合成isoLAB中使用的唯一保护基团。isoDAB是一种有效的和高度特异性的竞争性α-葡糖苷酶抑制剂（对于水稻α-葡糖苷酶，isoDAB的K（i）= 4 μ M，而DAB的K（i）为14 μ M）。isoDAB不是糖原磷酸化酶的抑制剂，而DAB是糖原磷酸化酶的有效抑制剂。这是碳支化亚氨基糖吡咯烷有效抑制糖苷酶的第一个例子。虽然isoLAB没有显示出对任何糖苷酶的抑制，但初步实验表明isoLAB部分挽救了缺陷的F508 del-CFTR功能，因此可能在囊性纤维化的研究中发挥作用。(C)2010爱思唯尔有限公司版权所有。
Acetonides are the only protecting groups used in the syntheses of isoDAB from D-ribose and of isoLAB from D-tagatose. isoDAB is a potent and highly specific competitive a-glucosidase inhibitor (for rice alpha-glucosidase, K(i) = 4 mu M for isoDAB compared to K(i) 14 mu M for DAB). isoDAB is not an whereas DAB is a potent inhibitor of glycogen phosphorylase. This is the first example of any potent inhibition of glycosidases by a carbon-branched iminosugar pyrrolidine. Although isoLAB shows no inhibition of any glycosidase, preliminary experiments suggest that isoLAB partially rescues the defective F508del-CFTR function and so may have a role in the study of cystic fibrosis. (C) 2010 Elsevier Ltd. All rights reserved.