methyl (2-azido-2-deoxy-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(β-D-glucopyranosyluronate)-(1→4)-(2-amino-2-deoxy-3,6-di-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2-O-sulfonato-α-L-idopyranosyluronate)-(1→4)-2-amino-2-deoxy-6-O-sulfonato-α-D-glucopyranoside sodium salt | 114870-02-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl (2-azido-2-deoxy-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(β-D-glucopyranosyluronate)-(1→4)-(2-amino-2-deoxy-3,6-di-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2-O-sulfonato-α-L-idopyranosyluronate)-(1→4)-2-amino-2-deoxy-6-O-sulfonato-α-D-glucopyranoside sodium salt
• 英文别名: methyl[2-amino-2-deoxy-6-O-sulfonato-α-D-glucopyranosyl]-(1→4)-[β-D-glucopyranosyluronate]-(1→4)-[2-amino-2-deoxy-3,6-di-O-sulfonato-D-glucopyranosyl]-(1→4)-[2-O-sulfonato-α-L-idopyranosyluronate]-(1→4)-2-amino-2-deoxy-6-O-sulfonato-α-D-glucopyranoside sodium salt；methyl O-2-amino-2-deoxy-6-O-sulfo-α-D-glucopyranosyl-(1-4)-O-2-O-hydroxyl-β-D-glucopyranosyluronosyl-(1-4)-O-2-amino-2-deoxy-3,6-di-O-sulfo-α-D-glucopyranosyl-(1-4)-O-2-O-sulfo-α-L-idopyranuronosyl-(1-4)-2-amino-2-deoxy-6-O-sulfo-α-D-glucopyranoside heptasodium salt
• CAS: 114870-02-9；119254-84-1
• 化学式: C₃₁H₄₆N₃O₄₀S₅*7Na
• 分子量: 1421.96
• InChiKey: ZTJATMGDYJGJPN-SKWQCJBYSA-G

计算性质

• 辛醇/水分配系数(LogP)：
  -19.43
• 重原子数：
  80.0
• 可旋转键数：
  24.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  704.15
• 氢给体数：
  9.0
• 氢受体数：
  43.0

反应信息

• 作为反应物：
  描述：

  methyl (2-azido-2-deoxy-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(β-D-glucopyranosyluronate)-(1→4)-(2-amino-2-deoxy-3,6-di-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2-O-sulfonato-α-L-idopyranosyluronate)-(1→4)-2-amino-2-deoxy-6-O-sulfonato-α-D-glucopyranoside sodium salt 在 pyridine*35SO₃ 、 三氧化硫吡啶 、 碳酸氢钠 作用下， 以 水 为溶剂， 以4%的产率得到
  参考文献：
  名称：

  Sperling, Eric; Heuvel, Marcel van den; Vader, Jan, Journal of Labelled Compounds and Radiopharmaceuticals, 1998, vol. 41, # 11, p. 1037 - 1038

  摘要：

  DOI：
• 作为产物：
  描述：

  methyl 2-deoxy-2-azido-3,4-di-O-benzyl-6-O-sulfo-α-D-glucopyranosyl-(1→4)-2,3-di-O-benzyl-β-D-glucopyrannuronosyl-(1→4)-2-deoxy-2-azido-3,6-di-O-sulfo-α-D-glucopyranosyl-(1→4)-3-O-benzyl-2-O-sulfo-α-L-idopyranuronosyl-(1→4)-2-deoxy-2-(carboxybenzylamino)-6-O-sulfo-α-D-glucopyranoside heptasodium salt 在 20% palladium hydroxide-activated charcoal 、 氢气 作用下， 以 甲醇 、 aq. phosphate buffer 为溶剂， 以85 %的产率得到methyl (2-azido-2-deoxy-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(β-D-glucopyranosyluronate)-(1→4)-(2-amino-2-deoxy-3,6-di-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2-O-sulfonato-α-L-idopyranosyluronate)-(1→4)-2-amino-2-deoxy-6-O-sulfonato-α-D-glucopyranoside sodium salt
  参考文献：
  名称：

  3,5-二甲基-4-(2′-苯基乙炔基苯基)苯基苷合成抗凝血五糖磺达肝素

  摘要：

  在这里，我们公开了一种制备 EPP [3,5-二甲基-4-(2'-苯基乙炔基苯基)苯基]糖苷的简便方法，及其在临床批准的抗凝肝素五糖磺达肝素的有效合成中的应用。利用EPP糖苷一锅法正交糖基化合成类肝素四糖也已实现。

  DOI：

  10.1021/acs.orglett.3c03484

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。
• PROCESS FOR PREPARING HEPARINOIDS AND INTERMEDIATES USEFUL IN THE SYNTHESIS THEREOF
  申请人：KOVI Ravishanker

  公开号：US20130005954A1

  公开（公告）日：2013-01-03

  Processes are disclosed for the synthesis of the Factor Xa anticoagulant fondaparinux and related compounds. Protected pentasaccharide intermediates and efficient and scalable processes for the industrial scale production of fondaparinux sodium by conversion of the protected pentasaccharide intermediates via a sequence of deprotection and sulfonation reactions are provided.

  公开了合成因子Xa抗凝剂磺达肝癸钠及其相关化合物的方法。提供了受保护的五糖中间体以及通过一系列去保护和磺化反应将受保护五糖中间体转化为磺达肝癸钠的工业规模生产的高效和可扩展过程。
• 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。
• EFFICIENT AND SCALABLE PROCESS FOR THE MANUFACTURE OF FONDAPARINUX SODIUM
  申请人：Patel Payal P.

  公开号：US20120116066A1

  公开（公告）日：2012-05-10

  The present invention relates to a process for the synthesis of the Factor Xa anticoagulent Fondaparinux and related compounds. The invention relates, in addition, to efficient and scalable processes for the synthesis of various intermediates useful in the synthesis of Fondaparinux and related compounds.

  本发明涉及一种合成因子Xa抗凝剂Fondaparinux及相关化合物的方法。此外，该发明还涉及一种高效且可扩展的合成过程，用于合成Fondaparinux及相关化合物中有用的各种中间体。
• Synthesis of heparin fragments: A methyl α-pentaoside with high affinity for antithrombin III
  作者：Maurice Petitou、Philippe Duchaussoy、Isidore Lederman、Jean Choay、Jean-Claude Jacquinet、Pierre Sinaÿ、Giangiacomo Torri

  DOI：10.1016/0008-6215(87)80268-9

  日期：1987.9

  The synthesis is described of the methyl alpha-glycoside of the pentasaccharide which represents the sequence in heparin responsible for binding and activation of the anticoagulant protein Antithrombin III. It was obtained in a yield much better than that of the previously synthesised pentasaccharide and exhibited the same biological properties.

  描述了五糖的甲基α-糖苷的合成，其代表肝素中负责结合和激活抗凝血蛋白Antithrombin III的序列。以比以前合成的五糖更好的产率获得了它，并表现出相同的生物学特性。