1,3,4,6-tetra-O-acetyl-2-deoxy-2-(tetrachlorophthalimido)-β-D-glucopyranose | 183388-14-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,3,4,6-tetra-O-acetyl-2-deoxy-2-(tetrachlorophthalimido)-β-D-glucopyranose
• 英文别名: 2-tetrachlorophthalimido β-D-glucose tetraacetate；1,3,4,6-tetra-O-acetyl-2-deoxy-2-tetrachlorophthalimido-β-D-glucopyranoside；[(2R,3S,4R,5R,6S)-3,4,6-triacetyloxy-5-(4,5,6,7-tetrachloro-1,3-dioxoisoindol-2-yl)oxan-2-yl]methyl acetate
• CAS: 183388-14-9
• 化学式: C₂₂H₁₉Cl₄NO₁₁
• 分子量: 615.205
• InChiKey: PAJWAARTNUUTKR-MSKCEUEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  152
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  1,3,4,6-tetra-O-acetyl-2-deoxy-2-(tetrachlorophthalimido)-β-D-glucopyranose 在 三氟化硼乙醚 、 sodium methylate 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 10.2h， 生成 4-methoxyphenyl 4,6-O-benzylidene-2-deoxy-2-(tetrachlorophthalimido)-β-D-glucopyranoside
  参考文献：
  名称：

  A High Yielding Chemical Synthesis of Sialyl Lewis x Tetrasaccharide and Lewis x Trisaccharide; Examples of Regio- and Stereodifferentiated Glycosylations

  摘要：

  Virtually complete regioselective galactosylation of the diol acceptor p-methoxyphenyl 6-O-benzyl-2-deoxy-2-tetrachlorophthalimido-beta-n-glucopyranoside (8) with the donor phenyl 2,3,4-tri-O-acetyl-6-O-benzyl-1-thio-beta-D-galactopyranoside (11) gave the lactosamine derivative 14, which was fucosylated with the donor 15 to give the Le(x) trisaccharide glycoside 2 after deprotection. Regioselective sialylation of the partially protected Le(x) trisaccharide triol 24 with the sialyl donor 25 gave, after deprotection, the SLe(x) tetrasaccharide glycoside 1. The overall yields of 2 and 1 from the monosaccharide starting materials 8, 11, 15, and 25 were 56% and 29%, respectively. In contrast to the virtually complete regio- and stereoselective galactosylation of 8, fucosylation with the benzyl-protected donor 15 gave the corresponding 1-->3- and 1-->4-linked disaccharides in a ratio of 3.6:1 (highly stereo- but not regioselective glycosylation), whereas fucosylation with acetyl-protected donor 18 gave a 2.2:1 beta/alpha-mixture of 4-O-linked disaccharides (highly regio- but not stereoselective glycosylation).

  DOI：

  10.1021/jo981203x
• 作为产物：
  描述：

  1,3,4,6-tetra-O-acetyl-2-deoxy-2-tetrachlorophthalimido-α-D-glucopyranoside 在 silver zeolite 、 氢溴酸 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 生成 1,3,4,6-tetra-O-acetyl-2-deoxy-2-(tetrachlorophthalimido)-β-D-glucopyranose
  参考文献：
  名称：

  Access to tetrachlorophthalimide-protected ethyl 2-amino-2-deoxy-1-thio-β-d-glucopyranosides

  摘要：

  Ethyl 2-deoxy-2-tetrachlorophthalimido-1-thio-beta-D-glucopyranoside (7) was prepared from glucosamine hydrochloride in four steps with a 20-25% overall yield. Formation of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-tetrachlorophthalimido-beta-D-glucopyranoside (5) was found to be crucial for this reaction sequence since the corresponding alpha-1-acetate did not react in Lewis-acid-catalyzed ethylthio glycosidations. Formation of the beta-1-acetate (5) was achieved by treatment of 3,4,6-tri-O-acetyl-2-deoxy-2-tetrachlorophthalimido-alpha-D-glucopyranosol bromide(4) with acetic acid under silver zeolite promotion. This was necessary because conditions normally used for p-l-acetate formation were not tolerated by the tetrachlorophthalimido (TCP) group. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0008-6215(98)00309-7

文献信息

• Synthesis of 5-Fluoro <i>N</i>-Acetylglucosamine Glycosides and Pyrophosphates via Epoxide Fluoridolysis:  Versatile Reagents for the Study of Glycoconjugate Biochemistry
  作者：Matthew C. T. Hartman、James K. Coward

  DOI：10.1021/ja0127234

  日期：2002.8.1

  catalysis via stabilization of positive charges on or near the C-1, C-4, C-5, or C-6 positions. Substrate analogues differing only in the substitution of a fluorine for the axial C-5 hydrogen would possess reduced electron density at these positions and could be useful mechanistic probes of these enzymes. Introduction of this 5-fluoro substituent after radical halogenation was problematic because of the incompatibility

  许多碳水化合物加工酶通过稳定 C-1、C-4、C-5 或 C-6 位置上或附近的正电荷来促进催化。仅在氟取代轴向 C-5 氢方面不同的底物类似物将在这些位置具有降低的电子密度，并且可能是这些酶的有用机械探针。在自由基卤化后引入这种 5-氟取代基是有问题的，因为许多保护基团与自由基卤化的不相容性以及随后的 5-氟己糖胺的不稳定性。因此，为了方便地获得各种 5-氟糖苷和糖基磷酸酯，开发了一种引入 5-氟基团的通用方法，关键步骤是 C-5, 6 环氧化物的氟化解。通过使用这种方法，已经合成了两种氟化碳水化合物，尿苷 5'-二磷酸-5-氟-N-乙酰氨基葡萄糖和辛基 5-氟-N-乙酰氨基葡萄糖。这些化合物的初步生化研究表明，5-氟类似物是几种酶催化反应中过渡态电荷发展的有用探针。
• Glycosyl Imidates, 76. Synthesis of Aryl C-Glycosides of Glucosamine
  作者：Julio C. Castro-Palomino、Richard R. Schmidt

  DOI：10.1002/jlac.199619961019

  日期：1996.10

  glucosamine donor 2 reacts with electron-rich phenol ethers 3a–c to afford aryl C-glycosides 4a–c. The N-tetrachlorophthaloyl group could be readily removed by sodium borohydride treatment and then phthalide formation or by treatment with ethylenediamine, respectively. The resulting product was subjected to reaction with acetic anhydride in pyridine to afford N,O-acetylated compounds 5a–c. After treatment

  所述Ñ -tetrachlorophthalimido保护的葡糖胺供体2种发生反应与富电子苯酚醚3A-C ，得到芳基C糖苷4a-c中。该Ñ -tetrachlorophthaloyl组可以由硼氢化钠处理，然后形成苯酞或通过处理而容易地除去与乙二胺，分别。使所得产物与乙酸酐在吡啶中反应，得到N，O-乙酰化的化合物5a–c。用乙二胺处理后，也可得到N，O-未保护的化合物，如6c所示。
• In vivo Neutralization of Naturally Existing Antibodies against Linear ?(1,3)-Galactosidic Carbohydrate Epitopes by Multivalent Antigen Presentation: A Solution for the First Hurdle of Pig-to-Human Xenotransplantation
  作者：Rudolf O. Duthaler、Beat Ernst、Reto Fischer、Andreas G. Katopodis、Willy Kinzy、Wolfgang Marterer、Reinhold Oehrlein、Markus B. Streiff、Gebhard Thoma

  DOI：10.2533/chimia.2010.23

  日期：——

  Pig-to-human xenotransplantation of islet cells or of vascularized organs would offer a welcome treatment alternative for the ever-increasing number of patients with end-stage organ failure who are waiting for a suitable allograph. The main hurdle are preexisting antibodies, most of which are specific for 'Linear-B', carbohydrate epitopes terminated by the unbranched Gal-?(1,3)Gal disaccharide. These antibodies are responsible for the 'hyper-acute rejection' of the xenograft by complement mediated hemorrhage. For depletion of such antibodies we have developed an artificial injectable antigen, a glycopolymer (GAS914) with a charge neutral poly-lysine backbone (degree of polymerization n = 1000) and 25% of its side chains coupled to Linear-B-trisaccharide. With an average molecular weight of 400 to 500 kD, presenting 250 trisaccharide epitopes per molecule, this multivalent array binds anti-?Gal antibodies with at least three orders of magnitude higher avidity on a per-saccharide basis than the monomeric epitope. In vivo experiments with non-human primates documented that rather low doses – 1 to 5 mg/kg of GAS914 injected i.v. – efficiently reduce the load of anti-Linear-B antibodies quickly by at least 80%. This treatment can be repeated without any sensitization to GAS914. Interestingly, although the antibody levels start raising 12 h after injection, they do not reach pretreatment levels. The polymer is degraded and excreted within hours, with a minute fraction remaining in lymphoid tissue of anti-?Gal producing animals only, probably binding to and inhibiting antibody-producing B-cells. The results of pig-to-non-human primate xenotransplantations established GAS914 as a relevant therapeutic option for pig-to-human transplantations as well. The synthesis of GAS914 was successfully scaled up to kg amounts needed for first clinical studies. Key was the use of galactosyl transferases and UDP-galactose for the synthesis of the trisaccharide.

  将猪到人体异种移植的胰岛细胞或血管化器官可为等待合适同种移植物的晚期器官功能衰竭患者提供一种受欢迎的治疗选择。主要障碍是已存在的抗体，其中大多数特异性针对以线性-B结尾的半乳糖-半乳糖二糖为终点的碳水化合物表位。这些抗体负责通过补体介导的出血引起的异种移植物的“超急性排斥”。为了清除这些抗体，我们开发了一种人工可注射抗原，一种具有电荷中性的聚赖氨酸骨架（聚合度n = 1000）和其25%的侧链偶联到线性-B三糖的糖聚合物（GAS914）。平均分子量为400至500千道因，每个分子呈现250个三糖表位，这种多价阵列以每糖基的至少三个数量级更高的亲和力结合抗-半乳糖抗体，而不是单体表位。非人灵长类动物的体内实验表明，注射i.v.的GAS914低剂量（1至5毫克/千克）能够迅速将至少80%的抗线性-B抗体负荷有效降低。这种治疗可以反复进行而不会对GAS914产生任何敏感性。有趣的是，尽管抗体水平在注射后12小时开始上升，但并未达到治疗前水平。聚合物在几小时内降解并排出体外，只有极小部分残留在仅产生抗-半乳糖的动物的淋巴组织中，可能与并抑制产生抗体的B细胞结合。猪到非人灵长类动物的异种移植结果将GAS914确立为猪到人体移植的相关治疗选择。GAS914的合成已成功扩大到首次临床研究所需的公斤级数量。关键是使用半乳糖转移酶和UDP-半乳糖合成三糖。
• C2-Symmetric bis-thioglycosides as new ligands for palladium-catalyzed allylic substitutions
  作者：Noureddine Khiar、Cristina S Araújo、Eleuterio Alvarez、Inmaculada Fernández

  DOI：10.1016/s0040-4039(03)00568-9

  日期：2003.4

  A new divergent design for the synthesis of optically pure bis-thioglycoside type I is reported. In only two steps a common chiral intermediate with up to eight free alcohols: two primary and six secondary is obtained. From this common intermediate a large number of ligands can be synthesized. A positional scanning like strategy has permitted the rapid discovery of an efficient catalyst for the palladium-catalyzed

  报道了一种新的发散设计，用于合成光学纯的I型双硫代糖苷。仅需两个步骤，即可获得具有多达八种游离醇的通用手性中间体：两个伯醇和六个仲醇。从这种常见的中间体可以合成大量的配体。类似位置扫描的策略已经允许快速发现钯催化的丙二酸酯的不对称烯丙基化的有效催化剂。Pd（II）配合物的动态NMR光谱显示，与钯配位后，对硫构型有有效的立体化学控制。