Methyl (benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)(1->4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside | 192505-56-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Methyl (benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)(1->4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside
• 英文别名: benzyl (2R,3S,4S,5R,6R)-3-hydroxy-4,5-dimethoxy-6-[(2R,3R,4S,5R,6S)-6-methoxy-4,5-bis(phenylmethoxy)-2-(phenylmethoxymethyl)oxan-3-yl]oxyoxane-2-carboxylate
• CAS: 192505-56-9
• 化学式: C₄₃H₅₀O₁₂
• 分子量: 758.863
• InChiKey: IVEHTRQKIGNRJD-YQIHFFSTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  55
• 可旋转键数：
  19
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  Methyl (benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)(1->4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside 在 吡啶 、 4-二甲氨基吡啶 、 溶剂黄146 、 三乙胺 、 硫脲 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 (benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1->4)-1,3,6-tri-O-acetyl-2-O-benzyl-D-glucopyranose
  参考文献：
  名称：

  Assessment through chemical synthesis of the size of the heparin sequence involved in thrombin inhibition

  摘要：

  Deca- to eicosasaccharides having the generic structure methyl(sodium 2,3-di-O-methyl-4-O-sodium sulfonato-alpha-L-idopyranosyluronate)-(1 --> 4)-[(2,3,6-tri-O-sodium sulfonato-alpha-D-glucopyranosyl)-(1 --> 4)-(sodium 2,3-di-O-methyl-alpha-L-idopyranosyluronate) -( 1 --> 4)](n)-2,3,6-tri-O-sodium sulfonato-alpha-D-glucopyranoside have been synthesized from a single disaccharide precursor. All of them bind to and activate antithrombin. When n less than or equal to 6 only Factor Xa inhibition is observed, whereas when n > 6 Factor Xa and thrombin are both inhibited in the presence of antithrombin. These results indicate that, in heparin, the sequence involved in antithrombin-catalyzed thrombin inhibition is a pentadecaor a hexadecasaccharide. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0008-6215(99)00068-3
• 作为产物：
  描述：

  methyl(2-O-benzoyl-4,6-O-isopropylidene-3-O-methyl-α-L-idopyranosyl)-(1->4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside 在 chromium(VI) oxide 、 4-二甲氨基吡啶 、 硫酸 、 水 、 sodium methylate 、 sodium hydride 、 potassium hydrogencarbonate 、 一水合肼 、 溶剂黄146 、 三乙胺 、 三氟乙酸 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 10.42h， 生成 Methyl (benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)(1->4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside
  参考文献：
  名称：

  Identification of a hexasaccharide sequence able to inhibit thrombin and suitable for ‘polymerisation’

  摘要：

  Three hexasaccharides, having from low to very high affinity for antithrombin, were synthesised from disaccharide building block precursors. One of them, methyl(sodium 2,3-di-O-methyl-4-O-sodium sulfonato-alpha-L-idopyranosyluronate)-(1 --> 4)-[(2,3,6-tri-O-sodium sulfonato-alpha-D-glucopyranosyl)-(1 --> 4)-(sodium 2,3-di-O-methyl-alpha-L-idopyranosyluronate)-(1 --> 4)](2)-2,3,6-tri-O-sodium sulfonato-alpha-D-glucopyranoside, obtainable from a single disaccharide building block precursor, constitutes a good starting point for obtaining simple oligosaccharidic heparin mimetics able to inhibit the two coagulation factors thrombin and Factor Xa. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0008-6215(99)00067-1

文献信息

• Synthesis of Conformationally Lockedl-Iduronic Acid Derivatives: Direct Evidence for a Critical Role of the Skew-Boat2S0 Conformer in the Activation of Antithrombin by Heparin
  作者：Sanjoy K. Das、Jean-Maurice Mallet、Jacques Esnault、Pierre-Alexandre Driguez、Philippe Duchaussoy、Philippe Sizun、Jean-Pascal Herault、Jean-Marc Herbert、Maurice Petitou、Pierre Sinaÿ

  DOI：10.1002/1521-3765(20011119)7:22<4821::aid-chem4821>3.0.co;2-n

  日期：2001.11.19

  of these three fixed conformations. A covalent two atom bridge between carbon atoms two and five of L-iduronic acid was first introduced to lock the pseudorotational itinerary of the pyranoid ring around the 2S0 form. A key compound to achieve this connection was the D-glucose derivative 5 in which the H-5 hydrogen atom has been replaced by a vinyl group, which is a progenitor of the carboxylic acid

  我们已经使用有机合成来了解L-艾杜糖酸构象柔韧性在肝素激活抗凝血酶中的作用。在代表肝素抗凝血酶结合位点的真正五糖序列的已知合成类似物中，我们选择了甲基化抗因子Xa五糖1作为参考化合物。与真正的原始片段一样，该分子的单个L-艾杜糖醛酸部分存在于水溶液中作为三个构象异构体1C4、4C1和2S0之间的平衡。因此，我们合成了1的三个类似物，其中L-艾杜糖醛酸单元被锁定在这三个固定构象之一中。首先引入在L-艾杜糖醛酸的两个碳原子和五个碳原子之间的共价两个原子桥，以将吡喃环的假旋转路线锁定在2S0形式周围。实现这种连接的关键化合物是D-葡萄糖衍生物5，其中H-5氢原子已被乙烯基取代，乙烯基是羧酸的祖先。对该分子的选择性操纵产生2S0型五糖23。从D-葡萄糖衍生物28开始，现在在碳原子3和5之间建立了一个共价的两个原子桥，以将L-艾杜糖酸部分锁定在1C4椅子周围形成1C4型五糖43。最后，由于在第5位上
• Experimental Proof for the Structure of a Thrombin-Inhibiting Heparin Molecule
  作者：Maurice Petitou、Anne Imberty、Philippe Duchaussoy、Pierre-Alexandre Driguez、Marie-Line Ceccato、Françoise Gourvenec、Philippe Sizun、Jean-Pascal Hérault、Serge Pérez、Jean-Marc Herbert

  DOI：10.1002/1521-3765(20010216)7:4<858::aid-chem858>3.0.co;2-n

  日期：2001.2.16

  Kinetic studies of thrombin inhibition by antithrombin in the presence of heparin have shown that thrombin binds to heparin in a preformed heparin - antithrombin complex. To study the relative position of the thrombin binding domain and the antithrombin binding domain on a heparin molecule we have designed and synthesized heparin mimetics which structurally are very similar to the genuine polysaccharide. Their inhibitory properties with respect to factor Xa and thrombin provide experimental evidence that in heparin the thrombin binding domain must be located at the nonreducing end of the antithrombin binding domain to observe thrombin inhibition. As expected, factor Xa inhibition is not affected by elongation of the antithrombin binding pentasaccharide sequence, regardless of the position in which this elongation takes place.
• Efficient synthesis of Idraparinux, the anticoagulant pentasaccharide
  作者：Chen Chen、Biao Yu

  DOI：10.1016/j.bmcl.2009.03.155

  日期：2009.7

  An efficient [DEF+GH] route was developed to the synthesis of Idraparinux, which is a fully O-sulfated, O-methylated mimic of the unique Antithrombin III binding domain of heparin. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and biological activity of a new anti-factor Xa pentasaccharide with a C-interglycosidic bond
  作者：Arnim Helmboldt、Maurice Petitou、Jean-Maurice Mallet、Jean-Pascal Hérault、Jean-Claude Lormeau、Pierre Alexandre Driguez、Jean-Marc Herbert、Pierre Sinaÿ

  DOI：10.1016/s0960-894x(97)00252-7

  日期：1997.6

  A mixed synthetic C, O-pentasaccharide 17 has been synthesized and shown to display an anti-factor Xa activity similar to that of the corresponding O-pentasaccharide 18. 17 represents the first example of a synthetic C-oligosaccharidic mimetic eliciting a significant biological response. (C) 1997 Elsevier Science Ltd.
• Introducing a C -interglycosidic bond in a biologically active pentasaccharide hardly affects its biological properties
  作者：Maurice Petitou、Jean-Pascal Hérault、Jean-Claude Lormeau、Arnim Helmboldt、Jean-Maurice Mallet、Pierre Sinaÿ、Jean-Marc Herbert

  DOI：10.1016/s0968-0896(98)00094-7

  日期：1998.9

  We describe here the synthesis and the biological activity of a 'C-pentasaccharide', a new analogue of the antithrombin III (AT III) binding region of heparin containing a methylene bridge in place of an interglycosidic oxygen atom. The affinity for AT III and the anti-factor Xa activity of this compound have been compared with that of the corresponding selected 'O-pentasaccharide'. Such a structural modification slightly decreased the affinity of this compound for AT III as well as its anti-factor Xa activity (880 +/- 40 anti-Xa units versus 1180 +/- 30 anti-Xa units for the C-pentasaccharide and the O-pentasaccharide, respectively). This compound therefore represents the first example of a new class of anti-factor Xa pentasaccharides containing a C-interglycosidic bond. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.