2,3,6-tri-O-benzyl-4-O-methyl-α,β-D-glucopyranose

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,3,6-tri-O-benzyl-4-O-methyl-α,β-D-glucopyranose
• 英文别名: 2,3,6-tri-O-benzyl-4-O-methyl-D-glucopyranose；(3R,4S,5R,6R)-5-methoxy-3,4-bis(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-ol
• 化学式: C₂₈H₃₂O₆
• 分子量: 464.558
• InChiKey: QLSXLMONBYHLQX-GJMNKMQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  66.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,3,6-tri-O-benzyl-4-O-methyl-α,β-D-glucopyranose 在 氢溴酸 、 氢气 、 palladium(II) hydroxide 、 lithium bromide 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 50.0~65.0 ℃ 、5.0 MPa 条件下， 反应 2.0h， 生成 5-(溴甲基)呋喃-2-甲醛
  参考文献：
  名称：

  从纤维素合成 5-溴甲基糠醛作为生物燃料的潜在中间体

  摘要：

  通过用 HBr 和 LiBr 处理并用甲苯连续萃取，纤维素可以转化为 5-溴甲基糠醛 (BMF)，这是一种全新的生物燃料或生物燃料中间体，产率为 80%。从其他碳水化合物和稻草中，也可以高产地获得 BMF。研究了 BMF 的形成机制，结果表明该糠醛是在纤维素解聚过程中形成的，葡萄糖不是中间体。

  DOI：

  10.1002/ejoc.201001539
• 作为产物：
  描述：

  methyl 2,3,6-tri-O-benzyl-4-O-methyl-α-D-glucopyranoside 在 盐酸 、 strontium (III) chloride hexahydrate 、 溶剂黄146 作用下， 以 水 为溶剂， 以45 %的产率得到2,3,6-tri-O-benzyl-4-O-methyl-α,β-D-glucopyranose
  参考文献：
  名称：

  基于结构的先导化合物优化可提高新型四氢咪唑并[1,2-a]吡啶-5-羧酸系列乙酰肝素酶-1抑制剂的效力和选择性

  摘要：

  Heparanase-1 (HPSE1) 是一种内切-β- d -葡萄糖醛酸酶，是唯一已知可裂解硫酸乙酰肝素蛋白聚糖 (HSPG) 的硫酸乙酰肝素 (HS) 的哺乳动物酶，而硫酸乙酰肝素蛋白聚糖是血管内皮基质糖萼层的关键成分。 HPSE1 的抑制具有治疗癌症和蛋白尿肾病的潜力。我们之前报道过2作为 HPSE1 抑制剂显示出中等效力，但对外切-β- d -葡萄糖醛酸酶 (GUSβ) 和葡萄糖脑苷脂酶 (GBA) 的选择性问题仍然存在。使用 X 射线共晶结构分析和碎片分子轨道计算对2进行基于结构的先导优化，得到4e ，其显示 HPSE1 抑制活性增加了 7 倍以上。随后将甲基引入4e的6-羟基中，导致18对GUSβ和GBA的抑制活性降低，同时保持对HPSE1的抑制活性。 18对小鼠血清HPSE1的抑制活性显着，在3、30和100 mg/kg剂量下持续4 h。化合物18可能是 HPSE1 抑制剂的新型先导化合物，具有改善的

  DOI：

  10.1016/j.bmc.2023.117460

文献信息

• Modified kojibiosides analogues
  申请人：Alberta Research Council

  公开号：US05633233A1

  公开（公告）日：1997-05-27

  Disclosed are novel analogues of kojibiose and pharmaceutical compositions comprising such analogues.

  公开的是曲酸的新颖类似物以及包含这些类似物的药物组合物。
• Modified
  申请人：Alberta Research Council

  公开号：US05929037A1

  公开（公告）日：1999-07-27

  Disclosed is the trisaccharide .alpha.-D-Glcp-(1-2)-.alpha.-D-Glcp-(1-3)-.alpha.-D-Glcp and compounds related thereto as well as pharmaceutical compositions thereof.

  揭示了三糖α-D-Glcp-(1-2)-α-D-Glcp-(1-3)-α-D-Glcp及其相关化合物以及其药物组合物。
• Inhibitors of <i>endo</i>-α-mannosidase. Part III. Congeners of 1-deoxy-3-<i>O</i>-(α-<scp>D</scp>-glucopyranosyl)-mannojirimycin modified in the glucose unit
  作者：Ulrike Spohr、Mimi Bach

  DOI：10.1139/v93-241

  日期：1993.11.1

  The syntheses of congeners of 1-deoxy-3-O-(α-D-glucopyranosyl)-mannojirimycin (1), a strong inhibitor of the glycoprotein-processing endo-mannosidase, are described. The chemical modifications of 1 involved all monodeoxy-genations and mono-O-methylations of the glucose unit and the replacement of this unit by D-galactose, D-xylose, and 2-chloro-2-deoxy-D-glucose. As reported previously, none of the modifications of 1, including deoxygenations and O- and N-methylations of the deoxymannojirimycin unit, improved the inhibitory properties, but demonstrated the high specificity in the recognition of 1 by the enzyme and allowed the assignment of intermolecular hydrogen bonds of the inhibitor • enzyme complex. Essential for complex formation were found NH-5, OH-2, OH-4, and OH-6 of the DMJ unit, as well as OH-3′, OH-4′, and CH₂-6′ of the glucose unit. The residual activities on deoxygenating the OH-2′ and OH-6′ groups of 1 suggest their involvement at the periphery of the binding site.

  描述了一种强烈抑制糖蛋白处理内切脱甲基酶的1-去氧-3-O-(α-D-葡萄糖吡喃基)-曼诺基霉素（1）同系物的合成。1的化学改性包括所有单去氧基化和单-O-甲基化葡萄糖单元以及将该单元替换为D-半乳糖、D-木糖和2-氯-2-脱氧-D-葡萄糖。正如先前报道的那样，1的所有改性，包括去氧化和去氧曼诺基霉素单元的O-和N-甲基化，都没有改善抑制性能，但表明了对酶识别1的高特异性，并允许分配抑制剂•酶复合物的分子间氢键。复合物形成所需的关键部位包括DMJ单元的NH-5、OH-2、OH-4和OH-6，以及葡萄糖单元的OH-3′、OH-4′和CH2-6′。对于1的OH-2′和OH-6′基团的去氧化残余活性表明它们参与了结合位点的外围。
• Chemical mapping of the active site of the glucoamylase of<i>Aspergillus niger</i>
  作者：Raymond U. Lemieux、Ulrike Spohr、Mimi Bach、Dale R. Cameron、Monica M. Palcic、Torben P. Frandsen、Bjarne B. Stoffer、Birte Svensson

  DOI：10.1139/v96-036

  日期：1996.3.1

  A recently developed technique for the probing of the combining sites of lectins and antibodies, to establish the structure of the epitope that is involved in the binding of an oligosaccharide, is used to study the binding of methyl α-isomaltoside by the enzyme glucoamylase. The procedure involved the determination of the effects on the kinetics of hydrolysis of both monodeoxygenation and mono-O-methylation at each of the seven hydroxyl groups in order to gain an estimate of the differential changes in the free energies of activation, ΔΔG^≠. As expected, from previous publications, both deoxygenation and O-methylation of OH-4 (reducing unit), OH-4′, or OH-6′ strongly hindered hydrolysis, whereas the kinetics were virtually unaffected by either the substitutions at OH-2 or structural changes at C-1. The substitutions at OH-3 caused increases of 2.1 and 1.9 kcal/mol in the ΔΔG^≠. In contrast, whereas deoxygenation of either OH-2′ or OH-3′ caused much smaller (0.96 and 0.52 kcal/mol) increases in ΔΔG^≠, the mono-O-methylations resulted in severe steric hindrance to the formation of the activated complex. The relatively weak effects of deoxygenation suggest that the hydroxyl groups are replaced by water molecules and thereby participate in the binding by contributing effective complementarity. Methyl α-isomaltoside was docked into the combining site of the X-ray crystal structure at 2.4 Å resolution of the complex with the inhibitor acarbose. A fit free of steric interactions with the protein was found that has the methyl α-glucopyranoside unit in the normal⁴C₁conformation and the other glucose unit approaching a half-chair conformation with the interunit fragment defined by the torsion angles [Formula: see text] The model provides a network of hydrogen bonds that appears to well represent the activated complex formed by the glucoamylase with both maltose and isomaltose since the structures appear to provide a sound rationale for both the specificity and catalysis provided by the enzyme. Key words: monodeoxy and mono-O-methyl derivatives of methyl α-isomaltoside, enzyme binding domain, functioning of glucoamylase, differential changes in free energy of activation, characteristics of hydrogen bonding networks.

  最近开发的一种技术用于探测凝集素和抗体的结合位点，以建立与寡糖结合中涉及的表位的结构，用于研究酶葡萄糖酶对甲基α-异麦芽糖的结合。该过程涉及确定对水解动力学的影响，包括每个七个羟基的单去氧和单-O-甲基化，以获得活化自由能的差异变化ΔΔG^≠的估计。如预期的那样，根据先前的发表，OH-4（还原单元）、OH-4'或OH-6'的脱氧和O-甲基化强烈阻碍了水解，而OH-2的置换或C-1的结构变化几乎不影响动力学。OH-3的置换导致ΔΔG^≠增加了2.1和1.9 kcal/mol。相比之下，OH-2'或OH-3'的脱氧导致ΔΔG^≠增加较小（0.96和0.52 kcal/mol），而单-O-甲基化导致了对激活复合物形成的严重位阻。脱氧的相对较弱影响表明，羟基被水分子取代，从而通过提供有效的互补性参与结合。甲基α-异麦芽糖被对接到X射线晶体结构的结合位点，分辨率为2.4 Å的复合物与抑制剂阿卡波糖。找到了与蛋白质无位阻相互作用的适合，其中甲基α-葡萄糖吡喃糖单元处于正常的4C1构象，另一个葡萄糖单元接近半椅构象，其间单元片段由扭转角度定义[Formula: see text]该模型提供了一个氢键网络，似乎很好地代表了由葡萄糖酶与麦芽糖和异麦芽糖形成的激活复合物，因为这些结构似乎为酶提供的特异性和催化提供了合理的基础。关键词：甲基α-异麦芽糖的单去氧和单-O-甲基衍生物，酶结合结构域，葡萄糖酶的功能，活化自由能的差异变化，氢键网络的特性。
• Synthesis of methyl 4′-O-methyl-13C12-β-d-cellobioside from 13C6-d-glucose. Part 1: Reaction optimization and synthesis
  作者：Yuko Yoneda、Toshinari Kawada、Thomas Rosenau、Paul Kosma

  DOI：10.1016/j.carres.2005.08.003

  日期：2005.10

  A high yielding synthetic route for methyl 4'-O-methyl-beta-D-cellobioside starting from d-glucose was established. The reaction conditions optimized with nonlabeled materials were used for the synthesis of methyl 4'-O-methyl-13C12-beta-D-cellobioside, a compound having more than 99% 13C enrichment at each of the twelve pyranose carbon atoms. The labeled compound is required to study the hydrogen bond

  建立了从d-葡萄糖开始的甲基4'-O-甲基-β-D-纤维二糖苷高产合成路线。使用未经标记的材料优化的反应条件用于合成甲基4'-O-甲基-13C12-β-D-纤维二糖苷，该化合物在十二个吡喃糖碳原子中的每一个上均具有超过99％的13C富集度。通过CPMAS NMR实验需要标记的化合物来研究纤维糊精和纤维素的氢键网络。