methyl 2,3,5-tri-O-benzyl-6-O-trityl-β-D-galactofuranoside | 920274-29-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: methyl 2,3,5-tri-O-benzyl-6-O-trityl-β-D-galactofuranoside
• 英文别名: (2R,3R,4S,5S)-2-methoxy-3,4-bis(phenylmethoxy)-5-[(1R)-1-phenylmethoxy-2-trityloxyethyl]oxolane
• CAS: 920274-29-9
• 化学式: C₄₇H₄₆O₆
• 分子量: 706.879
• InChiKey: RTMIUFQHMPHVBW-JQIFVRNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  53
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2,3,5-tri-O-benzyl-6-O-trityl-β-D-galactofuranoside 在 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 12.0h， 以85%的产率得到methyl 2,3,5-tri-O-benzyl-β-D-galactofuranoside
  参考文献：
  名称：

  Synthesis of a Pentasaccharide Fragment of Varianose, a Cell Wall Polysaccharide from Penicillium varians

  摘要：

  The first synthesis of an oligosaccharide fragment of varianose, a polysaccharide produced by Penicillium varians, is reported. The target pentasaccharide features both alpha- and beta-galactofuranoside residues and the alpha-galactofuranoside residue is hindered, being substituted on adjacent oxygens (O1 and O2), both of which are cis to the two-carbon side chain at C4. Key features of the synthesis include a novel method for the selective protection of the C3 hydroxyl group of galactofuranosyl residues via an epoxide formation/opening sequence, the introduction of the alpha-D-galactofuranosyl residue using a 2,3-anhydrosugar donor, and the use of the 1-benzenesulfinylpiperidine/trifluoromethanesulfonic anhydride activation method for the addition of an alpha-D-glucopyranosyl residue to a hindered hydroxyl group in an advanced tetrasaccharide intermediate.

  DOI：

  10.1021/jo061821a
• 作为产物：
  描述：

  溴甲苯 、 methyl-(O⁶-trityl-ξ-D-galactofuranoside) 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 12.0h， 生成 methyl 2,3,5-tri-O-benzyl-6-O-trityl-β-D-galactofuranoside 、 methyl 2,3,5-tri-O-benzyl-6-O-trityl-α-D-galactofuranoside
  参考文献：
  名称：

  Synthetic UDP-galactofuranose analogs reveal critical enzyme–substrate interactions in GlfT2-catalyzed mycobacterial galactan assembly

  摘要：

  分枝分散分得细胞壁的半乳糖聚合物由交替的β-(1→5)和β-(1→6)半乳糖呋喃糖残基组成，由两种双功能半乳糖呋喃糖转移酶GlfT1和GlfT2的作用组装而成，后者以UDP-半乳糖呋喃糖（UDP-Galf）作为供体底物。对合成的UDP-Galf类似物进行动力学分析确定了GlfT2（一个过程性聚合的糖苷转移酶）在识别供体底物时涉及的关键相互作用。对甲基化UDP-Galf类似物的测试表明，供体底物结合口袋在空间上显得拥挤。对脱氧UDP-Galf类似物的评估显示，C-6羟基并不是底物活性的必需部分，与UDP-Galf C-3羟基的相互作用可以使底物定向以便于转化，但似乎对底物识别没有作用，这使得3-脱氧类似物成为该酶的中等竞争抑制剂。此外，在生长的半乳糖链上添加在C-5或C-6去氧的Galf残基，或L-阿拉伯呋喃糖残基，都会导致“死锁”反应产物，这些产物不再作为酶的受体。该发现表明，GlfT2的活性需要同时识别受体底物的末端C-5和C-6羟基，这与最近基于该酶的晶体结构开发的模型一致。这些观察提供了对GlfT2活性位点中特异性蛋白质-碳水化合物相互作用的深入了解，并可能促进未来抑制剂的设计。

  DOI：

  10.1039/c2ob25159k

文献信息

• Synthetic UDP-galactofuranose analogs reveal critical enzyme–substrate interactions in GlfT2-catalyzed mycobacterial galactan assembly
  作者：Myles B. Poulin、Ruokun Zhou、Todd L. Lowary

  DOI：10.1039/c2ob25159k

  日期：——

  Mycobacterial cell wall galactan, composed of alternating β-(1→5) and β-(1→6) galactofuranosyl residues, is assembled by the action of two bifunctional galactofuranosyltransferases, GlfT1 and GlfT2, which use UDP-galactofuranose (UDP-Galf) as the donor substrate. Kinetic analysis of synthetic UDP-Galf analogs identified critical interactions involved in donor substrate recognition by GlfT2, a processive polymerizing glycosyltransferase. Testing of methylated UDP-Galf analogs showed the donor substrate-binding pocket is sterically crowded. Evaluation of deoxy UDP-Galf analogs revealed that the C-6 hydroxyl group is not essential for substrate activity, and that interactions with the UDP-Galf C-3 hydroxyl group orient the substrate for turnover but appears to play no role in substrate recognition, making the 3-deoxy-analog a moderate competitive inhibitor of the enzyme. Moreover, the addition of a Galf residue deoxygenated at C-5 or C-6, or an L-arabinofuranose residue, to the growing galactan chain resulted in “dead end” reaction products, which no longer act as an acceptor for the enzyme. This finding shows dual recognition of both the terminal C-5 and C-6 hydroxyl groups of the acceptor substrate are required for GlfT2 activity, which is consistent with a recent model developed based upon a crystal structure of the enzyme. These observations provide insight into specific protein–carbohydrate interactions in the GlfT2 active site and may facilitate the design of future inhibitors.

  分枝分散分得细胞壁的半乳糖聚合物由交替的β-(1→5)和β-(1→6)半乳糖呋喃糖残基组成，由两种双功能半乳糖呋喃糖转移酶GlfT1和GlfT2的作用组装而成，后者以UDP-半乳糖呋喃糖（UDP-Galf）作为供体底物。对合成的UDP-Galf类似物进行动力学分析确定了GlfT2（一个过程性聚合的糖苷转移酶）在识别供体底物时涉及的关键相互作用。对甲基化UDP-Galf类似物的测试表明，供体底物结合口袋在空间上显得拥挤。对脱氧UDP-Galf类似物的评估显示，C-6羟基并不是底物活性的必需部分，与UDP-Galf C-3羟基的相互作用可以使底物定向以便于转化，但似乎对底物识别没有作用，这使得3-脱氧类似物成为该酶的中等竞争抑制剂。此外，在生长的半乳糖链上添加在C-5或C-6去氧的Galf残基，或L-阿拉伯呋喃糖残基，都会导致“死锁”反应产物，这些产物不再作为酶的受体。该发现表明，GlfT2的活性需要同时识别受体底物的末端C-5和C-6羟基，这与最近基于该酶的晶体结构开发的模型一致。这些观察提供了对GlfT2活性位点中特异性蛋白质-碳水化合物相互作用的深入了解，并可能促进未来抑制剂的设计。
• Synthesis of a Pentasaccharide Fragment of Varianose, a Cell Wall Polysaccharide from <i>Penicillium varians</i>
  作者：Yu Bai、Todd L. Lowary

  DOI：10.1021/jo061821a

  日期：2006.12.1

  The first synthesis of an oligosaccharide fragment of varianose, a polysaccharide produced by Penicillium varians, is reported. The target pentasaccharide features both alpha- and beta-galactofuranoside residues and the alpha-galactofuranoside residue is hindered, being substituted on adjacent oxygens (O1 and O2), both of which are cis to the two-carbon side chain at C4. Key features of the synthesis include a novel method for the selective protection of the C3 hydroxyl group of galactofuranosyl residues via an epoxide formation/opening sequence, the introduction of the alpha-D-galactofuranosyl residue using a 2,3-anhydrosugar donor, and the use of the 1-benzenesulfinylpiperidine/trifluoromethanesulfonic anhydride activation method for the addition of an alpha-D-glucopyranosyl residue to a hindered hydroxyl group in an advanced tetrasaccharide intermediate.