methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside | 50605-04-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃二恶英
• 英文名称: methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside
• 英文别名: N-[(4aR,6R,7R,8R,8aS)-8-hydroxy-6-methoxy-2,2-dimethyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-7-yl]acetamide
• CAS: 50605-04-4
• 化学式: C₁₂H₂₁NO₆
• 分子量: 275.302
• InChiKey: NJXUELJWKHYHLF-ISUQUUIWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  86.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside 在 palladium on activated charcoal 三氟化硼乙醚 、 水 、 氢气 、 sodium methylate 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 76.0h， 生成 methyl α-D-glucopyranosyl-(1->4)-α-L-rhamnopyranosyl-(1->3)-2-acetamido-2-deoxy-β-D-glucopyranoside
  参考文献：
  名称：

  Synthesis of the Methyl Glycosides of a Di- and Two Trisaccharide Fragments Specific for theShigella flexneriSerotype 2aO-Antigen

  摘要：

  The stereocontrolled synthesis of methyl alpha-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranoside (EC, 1), methyl alpha-L-rhamnopyranosyl-(1-->3)-[alpha-D-glucopyra- osyl-(1-->4)]-alpha-L-rhamnopyranoside (B(E)C, 3) and methyl alpha-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->3)-2-acetamido-2-deoxy-beta-D-glucopyranoside (ECD, 4) is described; these constitute the methyl glycosides of branched and linear fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a. Emphasis was put on the construction of the 1,2-cis EC glycosidic linkage resulting in the selection of 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl fluoride (8) as the donor. Condensation of methyl 2,3-O-isopropylidene-4-O-trimethylsilyloside-alpha-L-rhamnopyranoside (11) and 8 afforded the fully protected alpha E-disaccharide 20, as a common intermediate in the synthesis of 1 and 3, together with the corresponding beta E-anomer 21. Deacetalation and regioselective benzoylation of 20, followed by glycosylation with 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (15) afforded the branched trisaccharide 25. Full deprotection of 20 and 25 afforded the targets 1 and 3, respectively. The corresponding beta E-disaccharide, namely, methyl beta-D-glucopyranosyl-(1-->4)-a-L-rhamnopyranoside (PEC, 2) was prepared analogously from 21. Two routes to trisaccharide 4 were considered. Route 1 involved the coupling of a precursor to residue E and a disaccharide CD. Route 2 was based on the condensation of an appropriate EC donor and a precursor to residue D. The former route afforded a 1:2 mixture of the alpha E and PE condensation products which could not be separated, neither at this stage, nor after deacetalation. In route 2, the required alpha E-anomer was isolated at the disaccharide stage and transformed into 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl-(1-->4)-2,3-di-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (48) as the EC donor. Methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-beta-D-glucopyran-oside (19) was preferred to its benzylidene analogue as the precursor to residue D. Condensation of 19 and 48 and stepwise deprotection of the glycosylation product afforded the target 4.

  DOI：

  10.1080/07328300008544123
• 作为产物：
  描述：

  2-methyl-(1,2-dideoxy-5,6-O-isopropylidene-β-D-glucofurano)[2,1-d]-2-oxazoline 在 camphor-10-sulfonic acid 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside
  参考文献：
  名称：

  作为登革热病毒拮抗剂的高效合成的Muramic和葡萄糖醛酸Glycodendrimers。

  摘要：

  碳水化合物通过糖-蛋白相互作用参与许多重要的病理过程，例如细菌和病毒感染。具有多种碳水化合物的糖缀合物参与多价相互作用，因此增加了它们与蛋白质的结合强度。在这项工作中，我们报告了新型的山武和葡萄糖醛酸糖树状聚合物作为潜在的登革热病毒拮抗剂的有效合成。通过点击化学，通过优化的合成策略，通过点击化学将具有末端乙炔基官能化的芳族支架偶联至村族和葡糖醛酸叠氮化物，从而以高收率提供所需的糖类树状聚合物。表面等离子体共振研究表明，所报道的化合物与登革热病毒包膜蛋白有效结合。进行了分子建模研究以模拟和解释观察到的结合。这些研究证实，可以轻松地实现糖类树状聚合物的有效化学合成，从而为寻找针对登革热病毒的新活性化合物提供了一种通用的策略。

  DOI：

  10.1002/chem.201903788

文献信息

• Total synthesis of a tetra- and two pentasaccharide fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a
  作者：Laurence A Mulard、Catherine Guerreiro

  DOI：10.1016/j.tet.2004.01.054

  日期：2004.3

  The synthesis of the methyl glycoside of the branched pentasaccharide biological repeating unit of the O-antigen of Shigella flexneri serotype 2a is described together with that of the methyl glycoside of the corresponding tetrasaccharide and frame-shifted linear pentasaccharide. All the strategies disclosed herein involve a key disaccharide corresponding to the branching point and otherwise appropriate

  描述了弗氏志贺氏菌血清型2a的O-抗原的分支五糖生物重复单元的甲基糖苷的合成以及相应的四糖和移码的线性五糖的甲基糖苷的合成。本文公开的所有策略都涉及对应于分支点的关键二糖和其他合适的被激活为其三氯乙酰亚胺酸酯的单糖结构单元。我们的数据表明，在分支残基处部分缺乏构象柔性。
• Selectively Charged and Zwitterionic Analogues of the Smallest Immunogenic Structure of Streptococcus Pneumoniae Type 14
  作者：Tiziana Gragnani、Doretta Cuffaro、Silvia Fallarini、Grazia Lombardi、Felicia D’Andrea、Lorenzo Guazzelli

  DOI：10.3390/molecules24183414

  日期：——

  Zwitterionic polysaccharides (ZPs) have been shown in recent years to display peculiar immunological properties, thus attracting the interest of the carbohydrate research community. To fully elucidate the mechanisms underlying these properties and exploit the potential of this kind of structures, in depth studies are still required. In this context, the preparation of two cationic, an anionic, as well as two zwitterionic tetrasaccharide analogues of the smallest immunogenic structure of Streptococcus pneumoniae type 14 (SP14) capsular polysaccharide are presented. By exploiting a block strategy, the negative charge has been installed on the non-reducing end of the lactose unit of the tetrasaccharide and the positive charge either on the non-reducing end of the lactosamine moiety or on an external linker. These structures have then been tested by competitive ELISA, showing that the structural variations we made do not modify the affinity of the neutral compound to binding to a specific antibody. However, lower efficacies than the natural SP14 compound were observed. The results obtained, although promising, point to the need to further elongate the polysaccharide structure, which is likely too short to cover the entire epitopes.

  最近几年，已经证明了离子交换多糖（ZPs）具有独特的免疫学特性，因此引起了碳水化合物研究界的关注。为了充分阐明这些特性的机制并利用这种结构的潜力，仍需要进行深入的研究。在这种情况下，介绍了两个阳离子，一个阴离子以及两个离子交换四糖类似物的最小免疫原性结构的制备。这些结构是链式的，负电荷被安装在四糖的乳糖单元的非还原端上，而正电荷则安装在乳糖胺基团的非还原端或外部连接剂上。然后，通过竞争性ELISA测试了这些结构，结果显示，我们所做的结构变化不会改变中性化合物与特定抗体结合的亲和力。然而，观察到比自然SP14化合物低的效能。虽然结果是有希望的，但它指出需要进一步延长多糖结构的长度，这很可能太短，无法覆盖整个表位。
• Convergent Synthesis, NMR and Conformational Analysis of Tetra- and Pentasaccharide Haptens of the Shigella flexneri Serotype 5a O-Specific Polysaccharide
  作者：Laurence A. Mulard、Marie-Jeanne Clément、Anne Imberty、Muriel Delepierre

  DOI：10.1002/1099-0690(200208)2002:15<2486::aid-ejoc2486>3.0.co;2-e

  日期：2002.8

  Convergent syntheses of the methyl glycosides of the branched pentasaccharide -L-Rhap-(12)-[-D-Glcp(13)]--L-Rhap-(13)--L-Rhap-(13)--D-GlcNAcp [A(E)BCD], featuring the biological repeating unit of the O-specific polysaccharide of Shigella flexneri serotype 5a, and of a related linear tetrasaccharide (EBCD) are described. The strategy, based on the trichloroacetimidate methodology, relied on the use

  分支五糖的甲基糖苷的聚合合成 -L-Rhap-(12)-[-D-Glcp(13)]--L-Rhap-(13)--L-Rhap-(13)--D-描述了 GlcNAcp [A(E)BCD]，其特征是志贺氏菌血清型 5a 的 O 特异性多糖和相关线性四糖 (EBCD) 的生物重复单元。该策略基于三氯乙酰亚胺方法，依赖于关键的 EB 二糖供体和适当的 CD 受体的使用。发现使用异亚丙基缩醛封闭残基 D 的 OH-4 和 OH-6 是使用更常用的亚苄基缩醛的合适替代方案。EBCD-OMe 和 A(E)BCD-OMe 的构象分析基于对 1H 和 13C 化学位移和通过 NMR 光谱获得的质子间距离数据的分析。数据显示残基 A 对残基 E 的构象行为没有影响，尽管这两个残基参与了 A(E)BCD-OMe 中的 2,3-顺式邻位糖基化模式。将两种寡糖的 1H 和 13C 化学位移与其对应序列的 S. flexneri
• Efficient Synthesis of Muramic and Glucuronic Acid Glycodendrimers as Dengue Virus Antagonists
  作者：Cecilia García‐Oliva、Alfredo H. Cabanillas、Almudena Perona、Pilar Hoyos、Ángel Rumbero、María J. Hernáiz

  DOI：10.1002/chem.201903788

  日期：2020.2.3

  interactions, thus increasing their binding strengths to proteins. In this work, we report the efficient synthesis of novel muramic and glucuronic acid glycodendrimers as potential Dengue virus antagonists. Aromatic scaffolds functionalized with a terminal ethynyl groups were coupled to muramic and glucuronic acid azides by click chemistry through optimized synthetic strategies to afford the desired glycodendrimers

  碳水化合物通过糖-蛋白相互作用参与许多重要的病理过程，例如细菌和病毒感染。具有多种碳水化合物的糖缀合物参与多价相互作用，因此增加了它们与蛋白质的结合强度。在这项工作中，我们报告了新型的山武和葡萄糖醛酸糖树状聚合物作为潜在的登革热病毒拮抗剂的有效合成。通过点击化学，通过优化的合成策略，通过点击化学将具有末端乙炔基官能化的芳族支架偶联至村族和葡糖醛酸叠氮化物，从而以高收率提供所需的糖类树状聚合物。表面等离子体共振研究表明，所报道的化合物与登革热病毒包膜蛋白有效结合。进行了分子建模研究以模拟和解释观察到的结合。这些研究证实，可以轻松地实现糖类树状聚合物的有效化学合成，从而为寻找针对登革热病毒的新活性化合物提供了一种通用的策略。
• Synthesis of the Methyl Glycosides of a Di- and Two Trisaccharide Fragments Specific for the<i>Shigella flexneri</i>Serotype 2a<i>O</i>-Antigen
  作者：Laurence A. Mulard、Corina Costachel、Philippe J. Sansonetti

  DOI：10.1080/07328300008544123

  日期：2000.1

  The stereocontrolled synthesis of methyl alpha-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranoside (EC, 1), methyl alpha-L-rhamnopyranosyl-(1-->3)-[alpha-D-glucopyra- osyl-(1-->4)]-alpha-L-rhamnopyranoside (B(E)C, 3) and methyl alpha-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->3)-2-acetamido-2-deoxy-beta-D-glucopyranoside (ECD, 4) is described; these constitute the methyl glycosides of branched and linear fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a. Emphasis was put on the construction of the 1,2-cis EC glycosidic linkage resulting in the selection of 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl fluoride (8) as the donor. Condensation of methyl 2,3-O-isopropylidene-4-O-trimethylsilyloside-alpha-L-rhamnopyranoside (11) and 8 afforded the fully protected alpha E-disaccharide 20, as a common intermediate in the synthesis of 1 and 3, together with the corresponding beta E-anomer 21. Deacetalation and regioselective benzoylation of 20, followed by glycosylation with 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (15) afforded the branched trisaccharide 25. Full deprotection of 20 and 25 afforded the targets 1 and 3, respectively. The corresponding beta E-disaccharide, namely, methyl beta-D-glucopyranosyl-(1-->4)-a-L-rhamnopyranoside (PEC, 2) was prepared analogously from 21. Two routes to trisaccharide 4 were considered. Route 1 involved the coupling of a precursor to residue E and a disaccharide CD. Route 2 was based on the condensation of an appropriate EC donor and a precursor to residue D. The former route afforded a 1:2 mixture of the alpha E and PE condensation products which could not be separated, neither at this stage, nor after deacetalation. In route 2, the required alpha E-anomer was isolated at the disaccharide stage and transformed into 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl-(1-->4)-2,3-di-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (48) as the EC donor. Methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-beta-D-glucopyran-oside (19) was preferred to its benzylidene analogue as the precursor to residue D. Condensation of 19 and 48 and stepwise deprotection of the glycosylation product afforded the target 4.