methyl 4-O-(2,3-di-O-benzyl-5-deoxy-5-methylthio-α-D-xylofuranosyl)-2,4,6-tri-O-benzyl-α-D-mannopyranoside | 887747-71-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 4-O-(2,3-di-O-benzyl-5-deoxy-5-methylthio-α-D-xylofuranosyl)-2,4,6-tri-O-benzyl-α-D-mannopyranoside
• 英文别名: methyl 2,3,6-tri-O-benzyl-4-O-(2,3-di-O-benzyl-5-deoxy-5-methylthio-D-xylofuranosyl)-α-D-mannopyranoside；Methyl 4-O-(2,3-di-O-benzyl-5-deoxy-5-methylthio-α-D-xylofuranosyl)-2,3,6-tri-O-benzyl-α-D-mannopyranoside；Bn(-2)[Bn(-3)][MeS(-5d)]Xylf(a1-4)[Bn(-2)][Bn(-3)][Bn(-6)]a-Man1Me；(2S,3S,4S,5R,6R)-2-methoxy-5-[(2S,3R,4R,5S)-5-(methylsulfanylmethyl)-3,4-bis(phenylmethoxy)oxolan-2-yl]oxy-3,4-bis(phenylmethoxy)-6-(phenylmethoxymethyl)oxane
• CAS: 887747-71-9
• 化学式: C₄₈H₅₄O₉S
• 分子量: 807.017
• InChiKey: ANWAEZAKNUBBLE-GADOLJCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  58
• 可旋转键数：
  21
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl 4-O-(2,3-di-O-benzyl-5-deoxy-5-methylthio-α-D-xylofuranosyl)-2,4,6-tri-O-benzyl-α-D-mannopyranoside 在 氨 、 sodium 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以89%的产率得到methyl 4-O-(5-deoxy-5-methylthio-α-D-xylofuranosyl)-α-D-mannopyranoside
  参考文献：
  名称：

  The 5-Deoxy-5-methylthio-xylofuranose Residue in Mycobacterial Lipoarabinomannan. Absolute Stereochemistry, Linkage Position, Conformation, and Immunomodulatory Activity

  摘要：

  Mycobacteria produce a cell-surface glycoconjugate, lipoarabinomannan (LAM), which has been shown to be a potent modulator of the immune response that arises from infection by these organisms. Recently, LAM from the human pathogens Mycobacterium tuberculosis and M. kansasii has been shown to contain an unusual 5-deoxy-5-methylthio-xylofuranose (MTX) residue as well as its corresponding oxidized counterpart, 5-deoxy-5-methylsulfoxy-xylofuranose (MSX). To date, the absolute configuration of these residues and their linkage position to the polysaccharide are unknown, as is their biological role. Through the combined use of chemical synthesis and NMR spectroscopy, we have established that the MTX/MSX residues in these glycoconjugates are of the D-configuration and that they are linked alpha-(1-4) to a mannopyranose residue in the mannan portion of the glycan. Conformational analysis of the MTX/MSX residue using NMR spectroscopy showed differences in ring conformation and as well as in the rotamer populations about the C-4-C-5 bond, as compared to the parent compound, methyl alpha-D-xylofuranoside. Two of the synthesized disaccharides, 3 and 34, were tested in cytokine induction assays, and neither led to the production of TNF-alpha or IL-12p70. In contrast, both demonstrated modest inhibitory properties when these same cytokines were induced using a preparation of Interferon-gamma and Staphylococcus aureus Cowan strain (SAC/IFN-gamma). These latter observations suggest that this motif may play a role in the immune response arising from mycobacterial infection.

  DOI：

  10.1021/ja057373q
• 作为产物：
  描述：

  p-tolyl 2,3-di-O-benzyl-5-O-toluenesulfonyl-1-thio-β-D-xylofuranoside 在 N-碘代丁二酰亚胺 、 18-冠醚-6 、 4 A molecular sieve 、 silver trifluoromethanesulfonate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 12.25h， 生成 methyl 4-O-(2,3-di-O-benzyl-5-deoxy-5-methylthio-α-D-xylofuranosyl)-2,4,6-tri-O-benzyl-α-D-mannopyranoside
  参考文献：
  名称：

  The 5-Deoxy-5-methylthio-xylofuranose Residue in Mycobacterial Lipoarabinomannan. Absolute Stereochemistry, Linkage Position, Conformation, and Immunomodulatory Activity

  摘要：

  Mycobacteria produce a cell-surface glycoconjugate, lipoarabinomannan (LAM), which has been shown to be a potent modulator of the immune response that arises from infection by these organisms. Recently, LAM from the human pathogens Mycobacterium tuberculosis and M. kansasii has been shown to contain an unusual 5-deoxy-5-methylthio-xylofuranose (MTX) residue as well as its corresponding oxidized counterpart, 5-deoxy-5-methylsulfoxy-xylofuranose (MSX). To date, the absolute configuration of these residues and their linkage position to the polysaccharide are unknown, as is their biological role. Through the combined use of chemical synthesis and NMR spectroscopy, we have established that the MTX/MSX residues in these glycoconjugates are of the D-configuration and that they are linked alpha-(1-4) to a mannopyranose residue in the mannan portion of the glycan. Conformational analysis of the MTX/MSX residue using NMR spectroscopy showed differences in ring conformation and as well as in the rotamer populations about the C-4-C-5 bond, as compared to the parent compound, methyl alpha-D-xylofuranoside. Two of the synthesized disaccharides, 3 and 34, were tested in cytokine induction assays, and neither led to the production of TNF-alpha or IL-12p70. In contrast, both demonstrated modest inhibitory properties when these same cytokines were induced using a preparation of Interferon-gamma and Staphylococcus aureus Cowan strain (SAC/IFN-gamma). These latter observations suggest that this motif may play a role in the immune response arising from mycobacterial infection.

  DOI：

  10.1021/ja057373q

文献信息

• IMMUNOMODULATORY SACCHARIDE COMPOUNDS
  申请人：Lowary L. Todd

  公开号：US20070219144A1

  公开（公告）日：2007-09-20

  Compounds comprising a saccharide molecule and a 5-deoxy-5-methylthio-xylofuranose (MTX) moiety or a 5-deoxy-5-methylsulfoxy-xylofuranose (MSX) moiety, and use of such compounds in methods for modulating inflammation and immune responses.

  包含糖分子和5-去氧-5-甲硫氧基-木糖呋喃糖（MTX）基团或5-去氧-5-甲基磺氧基-木糖呋喃糖（MSX）基团的化合物，以及在调节炎症和免疫反应方法中使用这些化合物。
• Neighbouring group participation vs. addition to oxacarbenium ions: studies on the synthesis of mycobacterial oligosaccharides
  作者：Susanne A. Stalford、Colin A. Kilner、Andrew G. Leach、W. Bruce Turnbull

  DOI：10.1039/b914417j

  日期：——

  methylsulfide group in the product. Model reactions indicated that the bicyclic intermediate would also act as a participating group to direct the acceptor alcohol to the lower α-face of the sugar. While the key sulfonium intermediate could be detected in the reaction mixture, the glycosylation reaction proceeded with moderate stereoselectivity, apparently via an SN1-type mechanism. Density functional

  邻居基团的参与经常用于控制化学反应的立体选择性。在本文中，我们调查了使用邻近基团参与结合分枝杆菌糖甲基硫代木糖的二糖的合成。通过甲基化将双环硫代糖苷活化，以生成甲基s基团，该甲基ulf基团既可以充当端基异构离去基团，又可以在产物中提供甲基硫醚基团。模型反应表明，双环中间体也将作为一个参与基团，将受体醇导向糖的较低α面。尽管可以在反应混合物中检测到关键的intermediate中间体，但糖基化反应仍以中等立体选择性进行，显然是通过S N进行的。1型机制。密度泛函理论计算被用于我们的methylthioxylose锍离子与比较一反-decalin状锍离子描述由恩惠和同事是一个α引导参与组（J.化学会会志。2005，127，12090 ）。我们的研究表明，即使可以在反应混合物中检测到双环sulf离子，在将其用作反应途径的中间体之前也应谨慎行事。