Synthesis of deoxygenated α(1 → 5)-linked arabinofuranose disaccharides as substrates and inhibitors of arabinosyltransferases of Mycobacterium tuberculosis
Synthesis of deoxygenated α(1 → 5)-linked arabinofuranose disaccharides as substrates and inhibitors of arabinosyltransferases of Mycobacterium tuberculosis
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DOI：
10.1016/j.bmc.2008.11.027
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发表时间：
2009-01-15
影响因子：
3.5
通讯作者：
Reynolds, Robert C.
中科院分区：
文献类型：
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作者：
Pathak, Ashish K.;Pathak, Vibha;Reynolds, Robert C.
阿拉伯糖基转移酶（Arabinosyltransferases，AraTs）在分枝杆菌细胞壁生物合成中起着重要作用，是治疗结核病，特别是耐多药分枝杆菌的潜在药物靶点。结核病（MTB）。在此，我们报道了在二糖的还原糖处具有脱氧作用的Araf α（1 -> 5）Araf二糖的合成和受体/抑制活性。在Araf的C-2或C-3位置处的脱氧通过使用羟基的黄原酸酯衍生物的自由基程序实现。通过将正辛基α-Araf 2-/3-脱氧、2-氟糖基受体与Araf硫代糖基供体偶联来产生α（1 -> 5）-连接的二糖。在无细胞分枝杆菌AraTs测定以及针对MTB H37 Ra和M.鸟复合体菌株。(C)2008爱思唯尔有限公司保留所有权利。
Arabinosyltransferases (AraTs) play a critical role in mycobacterial cell wall biosynthesis and are potential drug targets for the treatment of tuberculosis, especially multi-drug resistant forms of M. tuberculosis (MTB). Herein, we report the synthesis and acceptor/inhibitory activity of Araf alpha(1 -> 5) Araf disaccharides possessing deoxygenation at the reducing sugar of the disaccharide. Deoxygenation at either the C-2 or C-3 position of Araf was achieved via a free radical procedure using xanthate derivatives of the hydroxyl group. The alpha(1 -> 5)-linked disaccharides were produced by coupling n-octyl alpha-Araf 2-/3-deoxy, 2-fluoro glycosyl acceptors with an Araf thioglycosyl donor. The target disaccharides were tested in a cell free mycobacterial AraTs assay as well as an in vitro assay against MTB H37Ra and M. avium complex strains. (C) 2008 Elsevier Ltd. All rights reserved.