4-methylphenyl 6-O-acetyl-2-O-benzoyl-3-O-benzyl-1-thio-β-D-glucopyranoside | 1374561-81-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-methylphenyl 6-O-acetyl-2-O-benzoyl-3-O-benzyl-1-thio-β-D-glucopyranoside
• 英文别名: 4-tolyl 6-O-acetyl-2-O-benzoyl-3-O-benzyl-1-thio-β-D-glucopyranoside
• CAS: 1374561-81-5
• 化学式: C₂₉H₃₀O₇S
• 分子量: 522.619
• InChiKey: DEDDMUCIKNQDHT-QLZLUGFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.55
• 重原子数：
  37.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  91.29
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  4-methylphenyl 6-O-acetyl-2-O-benzoyl-3-O-benzyl-1-thio-β-D-glucopyranoside 在 吡啶 、 1,3-丙二硫醇 、 N-碘代丁二酰亚胺 、 2,2,6,6-四甲基哌啶氧化物 、 三氟甲磺酸三甲基硅酯 、 碘苯二乙酸 、 四丁基氟化铵 、 sodium methylate 、 三氧化硫-三乙胺复合物 、 magnesium methanolate 、 溶剂黄146 、 三乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 211.0h， 生成 sodium (methyl 4-O-(2-amino-4-O-benzyl-2-deoxy-3-O-(sodium sulfonato)-α-D-glucopyranosyl)-3-O-benzyl-β-D-glucopyranosid)uronate
  参考文献：
  名称：

  Divergent Synthesis of 48 Heparan Sulfate-Based Disaccharides and Probing the Specific Sugar–Fibroblast Growth Factor-1 Interaction

  摘要：

  Several biological processes involve glycans, yet understanding their ligand specificities is impeded by their inherent diversity and difficult acquisition. Generating broad synthetic sugar libraries for bioevaluations is a powerful tool in unraveling glycan structural information. In the case of the widely distributed heparan sulfate (HS), however, the 48 theoretical possibilities for its repeating disaccharide call for synthetic approaches that should minimize the effort in an undoubtedly huge undertaking. Here we employed a divergent strategy to afford all 48 HS-based disaccharides from just two orthogonally protected disaccharide precursors. Different combinations and sequence of transformation steps were applied with many downstream intermediates leading up to multiple target products. With the full disaccharide library in hand, affinity screening with fibroblast growth factor-1 (FGF-1) revealed that four of the synthetic sugars bind to FGF-1. The molecular details of the interaction were further clarified through X-ray analysis of the sugar-protein cocrystals. The capability of comprehensive sugar libraries in providing key insights in glycan-ligand interaction is, thus, highlighted.

  DOI：

  10.1021/ja3090065
• 作为产物：
  描述：

  4-甲基苯基1-硫代-2,3,4,6-四-O-(三甲基硅烷基)-beta-D-吡喃葡萄糖苷 在 三乙基硅烷 、 三氟甲磺酸三甲基硅酯 、 水 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 30.0h， 生成 4-methylphenyl 6-O-acetyl-2-O-benzoyl-3-O-benzyl-1-thio-β-D-glucopyranoside
  参考文献：
  名称：

  Divergent Synthesis of 48 Heparan Sulfate-Based Disaccharides and Probing the Specific Sugar–Fibroblast Growth Factor-1 Interaction

  摘要：

  Several biological processes involve glycans, yet understanding their ligand specificities is impeded by their inherent diversity and difficult acquisition. Generating broad synthetic sugar libraries for bioevaluations is a powerful tool in unraveling glycan structural information. In the case of the widely distributed heparan sulfate (HS), however, the 48 theoretical possibilities for its repeating disaccharide call for synthetic approaches that should minimize the effort in an undoubtedly huge undertaking. Here we employed a divergent strategy to afford all 48 HS-based disaccharides from just two orthogonally protected disaccharide precursors. Different combinations and sequence of transformation steps were applied with many downstream intermediates leading up to multiple target products. With the full disaccharide library in hand, affinity screening with fibroblast growth factor-1 (FGF-1) revealed that four of the synthetic sugars bind to FGF-1. The molecular details of the interaction were further clarified through X-ray analysis of the sugar-protein cocrystals. The capability of comprehensive sugar libraries in providing key insights in glycan-ligand interaction is, thus, highlighted.

  DOI：

  10.1021/ja3090065

文献信息

• [EN] SULFATION METHOD<br/>[FR] PROCÉDÉ DE SULFATATION
  申请人：UNIV GRIFFITH

  公开号：WO2019113646A1

  公开（公告）日：2019-06-20

  A method of N- or O-sulfation of a compound is described whereby the use of a co-solvent system comprising a participating component and a non-participating component, during the sulfation reaction, allows for the non-participating component to actively sequester the participating component away from the sulfated reaction product. This has benefits in decreasing the likelihood or extent of desulfation of the sulfated product and may result in precipitation of the sulfated product thereby allowing for simple collection.

  描述了一种N-或O-硫酸化化合物的方法，其中在硫酸化反应过程中使用共溶剂系统，该系统包括参与组分和非参与组分，允许非参与组分将参与组分从硫酸化反应产物中主动分离。这有利于降低硫酸化产品脱硫的可能性或程度，并可能导致硫酸化产品的沉淀，从而可以简单收集。
• Synthesis of the Heparin-Based Anticoagulant Drug Fondaparinux
  作者：Cheng-Hsiu Chang、Larry S. Lico、Teng-Yi Huang、Shu-Yi Lin、Chi-Liang Chang、Susan D. Arco、Shang-Cheng Hung

  DOI：10.1002/anie.201404154

  日期：2014.9.8

  Fondaparinux, a synthetic pentasaccharide based on the heparin antithrombin‐binding domain, is an approved clinical anticoagulant. Although it is a better and safer alternative to pharmaceutical heparins in many cases, its high cost, which results from the difficult and tedious synthesis, is a deterrent for its widespread use. The chemical synthesis of fondaparinux was achieved in an efficient and

  Fondaparinux是一种基于肝素抗凝血酶结合结构域的合成五糖，是公认的临床抗凝剂。尽管在许多情况下它是替代药物肝素的更好，更安全的替代方法，但由于合成困难而乏味，其高昂的成本阻碍了其广泛使用。磺达肝素的化学合成以有效和简洁的方式从可商购获得d -葡糖胺，二丙酮α- d葡萄糖和五-O-乙酰基d -葡萄糖。该方法涉及适当功能化的构建基块，这些构建基块易于使用，并使用共享的中间体和一系列单反应，从而显着减少了合成工作量并提高了收率。
• α-Glycosylation by <scp>d</scp>-Glucosamine-Derived Donors: Synthesis of Heparosan and Heparin Analogues That Interact with Mycobacterial Heparin-Binding Hemagglutinin
  作者：Medel Manuel L. Zulueta、Shu-Yi Lin、Ya-Ting Lin、Ching-Jui Huang、Chun-Chih Wang、Chiao-Chu Ku、Zhonghao Shi、Chia-Lin Chyan、Deli Irene、Liang-Hin Lim、Tsung-I Tsai、Yu-Peng Hu、Susan D. Arco、Chi-Huey Wong、Shang-Cheng Hung

  DOI：10.1021/ja302640p

  日期：2012.5.30

  Numerous biomolecules possess alpha-D-glucosamine as structural component. However, chemical glycosylations aimed at this backbone are usually not easily attained without generating the unwanted beta-isomer. We report herein a versatile approach in affording full alpha-stereoselectivity built upon a carefully selected set of orthogonal protecting groups on a D-glucosaminyl donor. The excellent stereoselectivity provided by the protecting group combination was found independent of leaving groups and activators. With the trichloroacetimidate as the optimum donor leaving group, core skeletons of glycosylphosphatidyl inositol anchors, heparosan, heparan sulfate, and heparin were efficiently assembled. The orthogonal protecting groups were successfully manipulated to further carry out the total syntheses of heparosan tri- and pentasaccharides and heparin di-, tetra-, hexa-, and octasaccharide analogues. Using the heparin analogues, heparin-binding hemagglutinin, a virulence factor of Mycobacterium tuberculosis, was found to bind at least six sugar units with the interaction notably being entropically driven.