(benzyl 4-O-levulinyl-2,3-di-O-methyl-α-L-idopyranosyluronate)-(1->4)-3,6-di-O-acetyl-2-O-benzyl-1-O-trichloroacetimidoyl-D-glucopyranose | 200712-66-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (benzyl 4-O-levulinyl-2,3-di-O-methyl-α-L-idopyranosyluronate)-(1->4)-3,6-di-O-acetyl-2-O-benzyl-1-O-trichloroacetimidoyl-D-glucopyranose
• CAS: 200712-66-9
• 化学式: C₃₉H₄₆Cl₃NO₁₆
• 分子量: 891.15
• InChiKey: PJOIRRWEGVGVPL-GTTPJQJISA-N

物化性质

• 沸点：
  817.636±75.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.420±0.14 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.32
• 重原子数：
  59.0
• 可旋转键数：
  18.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  210.73
• 氢给体数：
  1.0
• 氢受体数：
  17.0

反应信息

• 作为反应物：
  描述：

  (benzyl 4-O-levulinyl-2,3-di-O-methyl-α-L-idopyranosyluronate)-(1->4)-3,6-di-O-acetyl-2-O-benzyl-1-O-trichloroacetimidoyl-D-glucopyranose 、 methyl (benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1->4)-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1->4)-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1->4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside 在 4 A molecular sieve 、 叔丁基二甲硅基三氟甲磺酸酯 作用下， 以 甲苯 为溶剂， 反应 0.5h， 以64%的产率得到methyl (benzyl 4-O-levulinyl-2,3-di-O-methyl-α-L-idopyranosyluronate)-(1->4)-[(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1->4)-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1->4)]2-2,3,6-tri-O-benzyl-α-D-glucopyranoside
  参考文献：
  名称：

  First Synthetic Carbohydrates with the Full Anticoagulant Properties of Heparin

  摘要：

  A single disaccharide building block is required to obtain synthetic carbohydrates that reproduce the anticoagulant activity of heparin and inhibit thrombin (n>6) and/or factor Xa (n≥2; see reaction scheme). Thus, there is evidence that heparin fragments with at least 15 saccharide units are required for thrombin inhibition. Lev=levulinoyl.

  DOI：

  10.1002/(sici)1521-3773(19981116)37:21<3009::aid-anie3009>3.0.co;2-f
• 作为产物：
  描述：

  ethyl 2-O-benzoyl-4,6-O-isopropylidene-3-O-methyl-1-thio-L-idopyranoside 在 chromium(VI) oxide 、 4-二甲氨基吡啶 、 N-碘代丁二酰亚胺 、 三氟甲磺酸 、 4 A molecular sieve 、 硫酸 、 水 、 sodium methylate 、 sodium hydride 、 potassium carbonate 、 potassium hydrogencarbonate 、 C.I.酸性橙108 、 溶剂黄146 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 35.42h， 生成 (benzyl 4-O-levulinyl-2,3-di-O-methyl-α-L-idopyranosyluronate)-(1->4)-3,6-di-O-acetyl-2-O-benzyl-1-O-trichloroacetimidoyl-D-glucopyranose
  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

• 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.
• Assessment through chemical synthesis of the size of the heparin sequence involved in thrombin inhibition
  作者：Philippe Duchaussoy、Guy Jaurand、Pierre-A. Driguez、Isidore Lederman、Marie-L. Ceccato、Françoise Gourvenec、Jean-M. Strassel、Philippe Sizun、Maurice Petitou、Jean-M. Herbert

  DOI：10.1016/s0008-6215(99)00068-3

  日期：1999.4

  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.