methyl 2-azido-3-O-benzyl-2-deoxy-α-D-glucopyranoside | 175978-55-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2-azido-3-O-benzyl-2-deoxy-α-D-glucopyranoside
• 英文别名: Methyl 2-azido-3-O-benzoyl-2-deoxy-alpha-D-glucopyranoside；(2R,3S,4R,5R,6S)-5-azido-2-(hydroxymethyl)-6-methoxy-4-phenylmethoxyoxan-3-ol
• CAS: 175978-55-9
• 化学式: C₁₄H₁₉N₃O₅
• 分子量: 309.322
• InChiKey: CQGBJEFAUYCHSG-KSTCHIGDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 2-azido-3-O-benzyl-2-deoxy-α-D-glucopyranoside 在 20% palladium hydroxide-activated charcoal 、 氢气 、 三甲基铵三氧化硫共聚物 、 三乙胺 作用下， 以 aq. phosphate buffer 、 乙醇 、 水 为溶剂， 反应 16.0h， 生成 sodium salt of 2-deoxy-2-sulfoamino-β-D-glucopyranose
  参考文献：
  名称：

  Glycans as Ligands in Bioinorganic Chemistry. Probing the Interaction of a Trinuclear Platinum Anticancer Complex with Defined Monosaccharide Fragments of Heparan Sulfate

  摘要：

  We report herein a detailed NMR study of the aquation and subsequent covalent binding of the trinuclear clinical agent [{trans-PtCl((NH3)-N-15)(2)}(2){mu-trans-Pt((NH3)-N-15)(2)((NH2)-N-15(CH2)(6)(NH2)-N-15)(2)}](4+) (1, 1,0,1/t,t,t or Triplatin) with three d-glucosamine residues containing varied O-sulfate and N-sulfate or N-acetyl substitutions, which represent monosaccharide fragments present within the repeating disaccharide sequences of cell surface heparan sulfate (HS). The monosaccharides GlcNS(6S), GlcNS, and GlcNAc(6S) were synthesized in good yield from a common 4,6-diol alpha-methyl glucopyranoside intermediate. The reactions of N-15-1 with sodium sulfate, GlcNS(6S), GlcNS, and GlcNAc(6S) were followed by 2D [H-1,N-15] heteronuclear single quantum coherence (HSQC) NMR spectroscopy using conditions (298 K, pH approximate to 5.4) similar to those previously used for other anionic systems, allowing for a direct comparison. The equilibrium constants (pK(1)) for the aquation of 1 in the presence of GlcNS(6S) and GlcNS were slightly higher compared to that of the aquation in a sulfate solution, while a comparable pK(1) value was observed in the presence of GlcNAc(6S). A comparison of the rate constants for sulfate displacement of the aqua ligand showed preferential binding to 2-N-sulfate compared to 6-O-sulfate but a more rapid liberation. For disulfated GlcNS(6S), equilibrium conditions were achieved rapidly (9 h) and strongly favored the dichloro form, with <2% sulfato species observed. The value of k(L1) was up to 15-fold lower than that for binding to sulfate, whereas the rate constant for the reverse ligation (k(-L1)) was comparable. Equilibrium conditions were achieved much more slowly (similar to 100 h) for the reactions of 1 with GlcNS and GlcNAc(6S), attributed to covalent binding also to the N-donor of the sulfamate (GlcNS) group and the O-donor of the N-acetyl [GlcNAc(6S)] group. The rate constants (k(L2)) were 20-40-fold lower than that for binding to the 2-N- or 6-O-sulfate, but the binding was less reversible, so that their equilibrium concentrations (5-8%) were comparable to the 2-N- or 6-O-sulfate-bound species. The results emphasize the relevance of glycans in bioinorganic chemistry and underpin a fundamental molecular description of the HS-Pt interactions that alter the profile of platinum agents from cytotoxic to metastatic in a systematic manner.

  DOI：

  10.1021/acs.inorgchem.8b03035
• 作为产物：
  描述：

  methyl 2,3-anhydro-4,6-O-benzilidene-α-D-mannopyranoside 在 sodium azide 、 sodium hydride 、 三氟乙酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 methyl 2-azido-3-O-benzyl-2-deoxy-α-D-glucopyranoside
  参考文献：
  名称：

  [EN] AN EFFICIENT AND SCALABLE PROCESS FOR THE MANUFACTURE OF FONDAPARINUX SODIUM
  [FR] PROCÉDÉ EFFICACE ET EXTENSIBLE DE FABRICATION DE FONDAPARINUX SODIQUE

  摘要：

  本发明涉及一种用于合成因子Xa抗凝剂Fondaparinux及相关化合物的过程。此外，该发明还涉及用于合成Fondaparinux及相关化合物的各种中间体的高效可扩展过程。

  公开号：

  WO2013115817A1

文献信息

• Total Synthesis of Anticoagulant Pentasaccharide Fondaparinux
  作者：Tiehai Li、Hui Ye、Xuefeng Cao、Jiajia Wang、Yonghui Liu、Lifei Zhou、Qiang Liu、Wenjun Wang、Jie Shen、Wei Zhao、Peng Wang

  DOI：10.1002/cmdc.201400019

  日期：2014.5

  The anticoagulant pentasaccharide fondaparinux was synthesized using an improved and optimized synthetic strategy including a convergent [3+2] coupling approach, orthogonal protecting groups and various glycosyl donors. The new methods of glycosylation were also used for controlling the stereochemical configuration and improving the yield of the glycosylation. In addition, HPLC and NMR methods to monitor

  抗凝五糖磺达肝素是使用改进和优化的合成策略合成的，包括收敛的[3 + 2]偶联方法，正交保护基和各种糖基供体。糖基化的新方法也用于控制立体化学构型和提高糖基化的产率。另外，采用HPLC和NMR方法监测磺达肝素的全合成过程。这项工作在相关文献的基础上为磺达肝素的合成和分析提供了详尽的阐述，并为肝素样低聚糖的合成提供了丰富的信息。
• l-Iduronic acid derivatives as glycosyl donors
  作者：Christine Tabeur、Françoise Machetto、Jean-Maurice Mallet、Philippe Duchaussoy、Maurice Petitou、Pierre Sinaÿ

  DOI：10.1016/0008-6215(95)00346-0

  日期：1996.2

  O-[Methyl (2-O-acetyl-3-O-benzyl-4-O-levulinyl-alpha, and beta-L-idopyranosid)uronate] trichloroacetimidate and the corresponding n-pentenyl glycosides are efficient L-iduronic acid glycosyl donors. Both have been used for the high-yielding synthesis of basic disaccharide blocks which are useful for the subsequent synthesis of complex oligosaccharides related to heparin/heparan sulfate, and dermatan

  O-[（2-O-乙酰基-3-O-苄基-4-O-乙酰丙酰基-α-甲基和β-L-idopyranosid）尿酸甲酯]三氯乙亚胺酸酯和相应的n-戊烯基糖苷是有效的L-艾杜糖酸糖基供体。两者均已用于碱性二糖嵌段的高产率合成，其对于随后合成与肝素/硫酸乙酰肝素和硫酸皮肤素有关的复杂寡糖是有用的。相反，相应的硫代乙基糖苷，硫代苯基糖苷和氟化物未产生预期的二糖。
• 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。
• PROCESS FOR PREPARING FONDAPARINUX SODIUM AND INTERMEDIATES USEFUL IN THE SYNTHESIS THEREOF
  申请人：Nadji Sourena

  公开号：US20110105418A1

  公开（公告）日：2011-05-05

  Processes for the synthesis of the Factor Xa anticoagulent Fondaparinux, and related compounds are described. Also described are protected pentasaccharide intermediates as well as 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.

  描述了合成抗凝血因子Xa的抗凝剂Fondaparinux及其相关化合物的过程。还描述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的五糖中间体转化为Fondaparinux钠的高效可扩展工业规模生产过程。
• Synthetic heparin pentasaccharides
  申请人：ALCHEMIA LIMITED

  公开号：US09243018B2

  公开（公告）日：2016-01-26

  Preparation and use of synthetic monosaccharides, disaccharides, trisaccharides, tetrasaccharides and pentasaccharides useful for the preparation of synthetic heparinoids.

  合成单糖，双糖，三糖，四糖和五糖的制备和使用，用于合成肝素类化合物的制备。