methyl 6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-α-D-glucopyranoside | 175978-56-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-α-D-glucopyranoside
• 英文别名: methyl 2-azido-6-O-acetyl-3-O-benzyl-2-deoxy-α-D-glucopyranoside；[(2R,3S,4R,5R,6S)-5-azido-3-hydroxy-6-methoxy-4-phenylmethoxyoxan-2-yl]methyl acetate
• CAS: 175978-56-0
• 化学式: C₁₆H₂₁N₃O₆
• 分子量: 351.359
• InChiKey: NQMHZAAWTSSIIS-QCODTGAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  88.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-α-D-glucopyranoside 在 N-碘代丁二酰亚胺 、 2,2,6,6-四甲基哌啶氧化物 、 三氟甲磺酸三甲基硅酯 、 碘苯二乙酸 、 三氟乙酸 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 7.25h， 生成 methyl O-(methyl 2-O-levulinoyl-3-O-benzyl-α-L-idopyranosyluronate)(1→4)-O-2-azido-3-O-benzyl-6-O-acetyl-2-deoxy-α-D-glucopyranoside
  参考文献：
  名称：

  具有N-乙酰基和N-硫酸酯部分的硫酸乙酰肝素寡糖的模块合成

  摘要：

  硫酸乙酰肝素是结构多样的硫酸化多糖，存在于所有动物细胞的表面，在这里它们可以与多种蛋白质相互作用，从而调节广泛的生理和疾病过程。我们在这里描述了一种模块化的合成方法，该方法可以提供具有乙酰氨基葡萄糖残基的硫酸乙酰肝素寡糖文库，该残基被N-乙酰基和N-硫酸根部分的不同模式修饰。它基于使用在C2上被叠氮基或三氟甲基苯基甲亚胺部分修饰的糖基供体，从而可以选择性地安装α-糖苷。氨基保护基可以通过还原或酸处理选择性地被掩盖，从而可以安装N-乙酰基和N-硫酸根部分。与正交羟基保护基乙酰丙酸酯（Lev）酯，二甲基二甲基甲硅烷基（TDS）醚，碳酸烯丙氧基酯（Alloc）和碳酸9-芴基甲基酯（Fmoc）结合使用，可以安装不同类型的O-硫酸化。该方法用于制备四种N-和O-硫酸化方式不同的六糖。这些化合物与许多先前制备的HS寡糖一起被印刷为聚糖微阵列，以检查几种HS结合蛋白的结合选择性。

  DOI：

  10.1021/acs.joc.0c01881
• 作为产物：
  描述：

  1,5-anhydro-3-O-benzyl-4,6-O-benzylidene-2-deoxy-D-arabino-hex-1-enitol 在 吡啶 、 sodium azide 、 ammonium cerium(IV) nitrate 、 cesium fluoride 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 9.0h， 生成 methyl 6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-α-D-glucopyranoside
  参考文献：
  名称：

  L-艾杜糖酸衍生物作为糖基供体。

  摘要：

  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。

  DOI：

  10.1016/0008-6215(95)00346-0

文献信息

• Anomeric Reactivity-Based One-Pot Synthesis of Heparin-Like Oligosaccharides
  作者：Tülay Polat、Chi-Huey Wong

  DOI：10.1021/ja073098r

  日期：2007.10.1

  A highly efficient one-pot methodology is described for the synthesis of heparin and heparan sulfate oligosaccharides utilizing thioglycosides with well-defined reactivity as building blocks. L-Idopyranosyl and D-glucopyranosyl thioglycosides 5 and 10 were used as donors due to low reactivity of uronic acids as the glycosyl donors in the one-pot synthesis. The formation of uronic acids by a selective

  描述了一种高效的一锅法，利用具有明确反应活性的硫代糖苷作为构建模块来合成肝素和硫酸乙酰肝素寡糖。由于糖醛酸在一锅法合成中作为糖基供体的反应性较低，因此使用 L-吡喃糖基和 D-吡喃葡萄糖基硫代糖苷 5 和 10 作为供体。寡糖组装后，通过 C-6 选择性氧化形成糖醛酸。这种可编程策略的效率以及硫酸盐掺入的灵活性在二糖 17、18、四糖 23 和五糖 26 的代表性合成中得到了证明。
• Programmable One-Pot Synthesis of Heparin Pentasaccharide Fondaparinux
  作者：Supriya Dey、Hong-Jay Lo、Chi-Huey Wong

  DOI：10.1021/acs.orglett.0c01386

  日期：2020.6.19

  is considered to be better than the low-molecular weight heparin in terms of anticoagulation response, duration of action, and biosafety. However, the synthetic methods previously developed for its manufacture are relatively complicated, thus restricting its extensive use. We report here a potentially scalable and programmable one-pot synthesis of Fondaparinux using the [1,2,2] strategy and designed

  自2002年以来，经临床批准的Fondaparinux（Arixtra）已用于治疗深静脉血栓形成和急性肺栓塞，在抗凝反应，作用时间和生物安全性方面均被认为优于低分子量肝素。然而，先前开发用于其制造的合成方法相对复杂，因此限制了其广泛使用。我们在这里报告了一种使用[1,2,2]策略进行Fondaparinux的潜在可扩展和可编程的一锅合成方法，并设计了具有明确定义的反应性的硫代糖苷作为结构单元。
• Programmable one-pot synthesis of heparin pentasaccharides enabling access to regiodefined sulfate derivatives
  作者：Supriya Dey、Chi-Huey Wong

  DOI：10.1039/c8sc01743c

  日期：——

  HS/H contributes most significantly to the structural diversity and binding interactions. However, the synthesis of HS with defined sulfation patterns remains a major challenge. Herein, we report a highly efficient and programmable one-pot method for the synthesis of protected heparin pentasaccharides using thioglycoside building blocks with optimized relative reactivities to allow the selective deprotection

  肝素 (H) 和硫酸乙酰肝素 (HS) 属于寡糖糖胺聚糖 (GAG) 家族，已知它们的序列和硫酸化模式可调节生物过程中各种蛋白质的功能。其中，HS/H 的 6- O-硫酸化对结构多样性和结合相互作用的贡献最为显着。然而，合成具有明确硫酸化模式的 H2S 仍然是一个重大挑战。在此，我们报告了一种高效且可编程的一锅法，使用具有优化的相对反应性的硫代糖苷结构单元合成受保护的肝素五糖，以允许选择性脱保护和制备区域定义的硫酸盐衍生物。
• Development of specific inhibitors for heparin-binding proteins based on the cobra cardiotoxin structure: an effective synthetic strategy for rationally modified heparin-like disaccharides and a trisaccharide
  作者：Weijun Ke、Dennis M. Whitfield、Jean-Robert Brisson、Gary Enright、Harold C. Jarrell、Wen-guey Wu

  DOI：10.1016/j.carres.2004.11.029

  日期：2005.2

  Recently, a new heparin disaccharide-binding site on the convex side of cobra cardiotoxin (CTX) was identified by NMR spectroscopy and molecular modeling. To further characterize this site two heparin-like disaccharides were synthesized for binding studies with CTX, and a trisaccharide was synthesized for testing the sequence of the disaccharide binding to CTX. Thus six differentially protected monosaccharide building blocks (three L-iduronic acids and three D-glucosamines) were prepared. These include a L-iduronic acid elongation building block namely methyl 2-O-acetyl-4-O-levulinoyl-3-O-pivaloyl-alpha-L-idopyranosyluronate trichloroacetimidate for which a single-crystal X-ray structure was determined to have M-r = 576.79, a = 9.3098(11) Angstrom alpha = 90degrees, b = 10.3967(12) Angstrom beta = 90degrees, c = 28.026(3) Angstrom gamma = 90degrees, V = 2712.7(6) Angstrom(3), P2(1)2(1)2(1), Z = 4, mu = 0.71073 Angstrom, and R = 0.0378 for 7586 observed reflections. It shows that the molecular structure of the donor is in the C-1(4) conformation with significant 1,3-diaxial interactions between O-1 and O-3 as well as O-2 and O-4. The disaccharides and trisaccharide vary in the degree and position of O- and N-sulfation. The pivaloyl group was used as permanent protecting group of hydroxyl. The levulinoyl group was used as the temporary protecting group to protect the hydroxyl for elongation. Crown Copyright (C) 2005 Published by Elsevier Ltd. All rights reserved.
• A short route to l-iduronic acid building blocks for the syntheses of heparin-like disaccharides
  作者：Weijun Ke、Dennis M Whitfield、Manjinder Gill、Suzon Larocque、Siu-Hong Yu

  DOI：10.1016/j.tetlet.2003.08.092

  日期：2003.10

  The effective preparation of differentially protected L-iduronic acid derivatives, as building blocks for the synthesis of heparin-like oligosaccharides, is described in less than nine steps starting from readily available 1,2-O-isopropylidene-6,3-D-glucuronolactone. The pivaloyl group was used as a permanent protecting group of hydroxyl groups. Two heparin-like disaccharides with different sulfation pattern have been prepared by using these L-iduronic acid building blocks. Crown Copyright (C) 2003 Published by Elsevier Ltd. All rights reserved.