allyl 2,3,4-tri-O-acetyl-α-D-glucopyranosiduronic acid | 799280-67-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: allyl 2,3,4-tri-O-acetyl-α-D-glucopyranosiduronic acid
• 英文别名: (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-prop-2-enoxyoxane-2-carboxylic acid
• CAS: 799280-67-4
• 化学式: C₁₅H₂₀O₁₀
• 分子量: 360.318
• InChiKey: SJMSHTIWMJVJEY-BAYHKCFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  135
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  allyl 2,3,4-tri-O-acetyl-α-D-glucopyranosiduronic acid 在 草酰氯 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.25h， 生成 N,N'-bis(quinoxalin-2-ylmethyl)-N,N'-[1,4-phenylenebis(methylene)]bis-(allyl 2,3,4,tri-O-acetyl-α-D-glucopyranosiduronamide)
  参考文献：
  名称：

  通过将喹喔啉残基嫁接到糖基支架上来制备棘轮霉素类似物

  摘要：

  棘霉素是一种天然的双缩肽，它是一种双嵌入剂，可优先在DNA的CG碱基对附近插入喹喔啉单元。在本文中，提出了基于两个喹喔啉残基接枝到大环支架（乙二醇）上的棘霉素模拟物的设计和合成。使用紫外可见光谱和稳态荧光光谱以及热变性研究了化合物与小牛胸腺DNA的结合。有趣的观察结果是拟肽模拟物与DNA结合后荧光发射增强，这与棘霉素的观察结果相反。利用分子动力学模拟来更详细地探索其中一种糖蜜是否可能双向插入DNA。发现在298 K的20 ns模拟过程中，带有DNA的双插层棘皮霉素复合物是稳定的。然而，与DNA八聚体复合的糖基的MD模拟显示出与棘霉素的行为截然不同，并且发现其喹喔啉单元迅速从嵌入位点迁移出来。在整个模拟过程中，只有一个喹喔啉生色团保持嵌入状态，从而释放了双嵌入菌株。MD模拟结束时，糖烷中喹喔啉残基之间的距离为7.3-7.5Å，而在棘球霉素中，残基之间的距离为约11Å，这表明需要更长的糖基支架

  DOI：

  10.1016/j.bmc.2010.12.009
• 作为产物：
  描述：

  (allyloxy)triethylsilane 、 2,3,4-tri-O-acetyl-β-D-glucopyranurono-6,1-lactone 在 四氯化锡 作用下， 以 二氯甲烷 为溶剂， 以92%的产率得到allyl 2,3,4-tri-O-acetyl-α-D-glucopyranosiduronic acid
  参考文献：
  名称：

  Metathesis of Structurally Preorganized Bivalent Carbohydrates. Synthesis of Macrocyclic and Oligomeric Scaffolds

  摘要：

  [GRAPHICS]Bivalent carbohydrate substrates for metathesis were synthesized from glucuronic acid and phenylene-1,4-diamine. The substrate secondary structure depends on whether secondary or tertiary amides are present, and this influences the course of the metathesis reaction leading to novel multivalent scaffolding. Molecular modeling suggests that a very rigid macrocyclic scaffold has potential for the development of alpha-helix peptidomimetics.

  DOI：

  10.1021/ol0484254

文献信息

• Synthesis of Bivalent Lactosides Based on Terephthalamide, <i>N</i>,<i>N</i>′-Diglucosylterephthalamide, and Glycophane Scaffolds and Assessment of Their Inhibitory Capacity on Medically Relevant Lectins
  作者：Rosaria Leyden、Trinidad Velasco-Torrijos、Sabine André、Sebastien Gouin、Hans-Joachim Gabius、Paul V. Murphy

  DOI：10.1021/jo901667r

  日期：2009.12.4

  glucuronic acid derivative and p-xylylenediamine with subsequent ring-closing metathesis. Finally, a more flexible bivalent lactoside was produced from lactosyl azide with use of the copper-catalyzed azide−alkyne cycloaddition. Distances between lactose residues were analyzed computationally as were their orientations for the relatively rigid subset of compounds. Distinct spacing properties were revealed by

  凝集素对聚糖的识别可启动临床上相关的过程，例如毒素结合或肿瘤扩散。因此，开发有效的抑制剂具有医学前景。为了实现这一目标，我们报告了在包括仲和叔对苯二甲酰胺和N，N'-二葡萄糖基对苯二甲酰胺的支架上合成刚性和柔性二价乳糖苷的方法。这些化合物的构建涉及施密特-米歇尔（Schmidt-Michel）糖基化，以及关键步骤中相关糖胺的酰胺偶联或Ugi反应。也从葡糖醛酸衍生物和的偶合制备的基于刚性glycophane甲glycocluster p-二甲苯二胺及其后的闭环复分解反应。最后，使用铜催化的叠氮化物-炔烃环加成反应，由乳糖基叠氮化物生产了更具挠性的二价乳糖苷。通过计算分析乳糖残基之间的距离，以及化合物相对刚性子集的乳糖残基的方向。通过改变支架的结构或通过改变乳糖残基在支架上的位置来揭示不同的间隔性质。为了将这些特征与生物活性相关联，在三种类型的测定中，将植物毒素和人类黏附/生长调节半乳糖凝素用
• Phenylenediamine-based bivalent glycocyclophanes: synthesis and analysis of the influence of scaffold rigidity and ligand spacing on lectin binding in cell systems with different glycomic profiles
  作者：Sabine André、Trinidad Velasco-Torrijos、Rosaria Leyden、Sebastien Gouin、Manuela Tosin、Paul V. Murphy、Hans-Joachim Gabius

  DOI：10.1039/b913010a

  日期：——

  The conjugation of carbohydrates to synthetic scaffolds has the goal of preparing potent inhibitors of lectin binding. We herein report the synthesis of a panel of bivalent compounds (cyclophane and terephthalamide-derivatives) then used to establish the influence of scaffold flexibility on respective inhibitory potency in a medically relevant test system. Synthetic routes to two phenylenediamine-based glycocyclophanes involving Ugi reactions of glucuronic acid derivatives and subsequent ring closing metathesis are described, as are improvements for producing terephthalamide-based carbohydrate carriers. Assays were performed with human tumour cells measuring quantitatively the influence of the test compounds on fluorescent surface staining by labelled lectins. Biological evaluation using two different lines of cancer cells as well as cells with known alterations in the glycomic profile (cells treated with an inhibitor of glycan processing and a glycosylation mutant) reduced the risk of generating premature generalizations regarding inhibitor potency. Bioactivity relative to free mannose was invariably determined for the synthetic compounds. A clear trend for enhanced inhibitory properties for macrocyclic compounds compared to non-macrocyclic derivatives was discerned for one type of glycocyclophane. Herein we also document the impact of altering the spacing between the mannose residues, altering cell surface ligand density and cell-type reactivity. The applied strategy for the cell assays is proposed to be of general importance in the quest to identify medically relevant lectin inhibitors.

  将碳水化合物与合成支架共轭的目的是制备有效的凝集素结合抑制剂。我们在此报告了一组二价化合物（环烷和对苯二甲酰胺-衍生物）的合成过程，然后用来确定支架的灵活性在医学相关测试系统中对各自抑制效力的影响。文中介绍了两种苯二胺基糖环烷的合成路线，包括葡萄糖醛酸衍生物的乌基反应和随后的闭环偏析，以及生产对苯二甲酰胺基碳水化合物载体的改进方法。用人类肿瘤细胞进行了试验，定量测量了试验化合物对标记凝集素荧光表面染色的影响。使用两种不同的癌细胞系以及已知糖型改变的细胞（使用糖加工抑制剂和糖基化突变体处理的细胞）进行生物评估，降低了过早概括抑制剂效力的风险。合成化合物相对于游离甘露糖的生物活性始终是确定的。与非大环衍生物相比，一种类型的糖环烷明显具有增强大环化合物抑制性的趋势。在此，我们还记录了改变甘露糖残基间距、改变细胞表面配体密度和细胞类型反应性的影响。我们提出的细胞试验应用策略在寻找医学相关凝集素抑制剂的过程中具有普遍意义。
• Synthesis and conformational analysis of novel water soluble macrocycles incorporating carbohydrates, including a β-cyclodextrin mimic
  作者：Trinidad Velasco-Torrijos、Paul V. Murphy

  DOI：10.1016/j.tetasy.2004.11.020

  日期：2005.1

  Rigid macrocyclic scaffolds based on carbohydrates have potential for the display of recognition groups with defined 3D structure and may have application in bioorganic and supramolecular chemistry. A series of water soluble macrocyclic structures containing two saccharide units was synthesised by ring closing metathesis of allyl and pentenyl glycosides derived from glucuronic acid. The 3D structure of the constrained systems was explored by NMR and computational methods. CD spectra were also recorded. On the basis of experimental observations we suggest that the carbohydrate presentation is constrained into a U-shape for the smaller ring size but can access an S-shape arrangement in the larger macrocycle. As an extension it is shown that the larger macrocycle displayed phenomena similar to beta-cyclodextrin (beta-CD). The binding of 8-anilino-1-naphthalenesulfonate (ANS) to beta-CD is detectable by reversal of quenching of the ANS emission spectrum and a similar reversal of quenching was observed when this macrocycle was added to a solution of ANS; this was further supported by NMR. Furthermore molecular modelling suggests that the macrocyclic scaffolding has potential for the development of peptidomimetics. (C) 2004 Elsevier Ltd. All rights reserved.