ethyl 4-O-acetyl-2,6-di-O-benzoyl-1-thio-β-D-galactopyranoside | 203514-18-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 4-O-acetyl-2,6-di-O-benzoyl-1-thio-β-D-galactopyranoside
• 英文别名: ethyl 4-O-acetyl-2,6-di-O-benzyl-1-thio-β-D-galactopyranoside；ethyl 4-O-acetyl-2,6-di-O-benzoyl-β-D-galactopyranoside；[(2R,3R,4S,5R,6S)-3-acetyloxy-5-benzoyloxy-6-ethylsulfanyl-4-hydroxyoxan-2-yl]methyl benzoate
• CAS: 203514-18-5
• 化学式: C₂₄H₂₆O₈S
• 分子量: 474.532
• InChiKey: MWTAHSNKDAUWFJ-ZTGMJEERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 4-O-acetyl-2,6-di-O-benzoyl-1-thio-β-D-galactopyranoside 在 sodium methylate 、 copper(II) bis(trifluoromethanesulfonate) 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 41.0h， 生成 (1R,2R,4S,6R)-4-Azidomethyl-6-[(2R,3R,4S,5S,6R)-3,5-dihydroxy-6-hydroxymethyl-4-((2R,3R,4S,5S,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yloxy]-cyclohexane-1,2,4-triol
  参考文献：
  名称：

  Synthesis of Gal determinant epitopes, their glycomimetic variants, and trimeric clusters—relevance to tumor associated antigens and to discordant xenografts

  摘要：

  The synthesis of Gal alpha1 --> 3Gal-quinic acid pseudo-trisaccharides and their elaboration into trimeric clusters is described. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(01)00195-8
• 作为产物：
  描述：

  乙基-2,6-二-氧-苯甲酰基-3,4-氧-异丙叉-Β-D-硫代吡喃半乳糖苷 在 对甲苯磺酸 作用下， 以 溶剂黄146 、 苯 为溶剂， 反应 2.0h， 生成 ethyl 4-O-acetyl-2,6-di-O-benzoyl-1-thio-β-D-galactopyranoside
  参考文献：
  名称：

  Sarbajna, Sumita; Roy, Nirmolendu, Carbohydrate Research, 1998, vol. <1-2> 306, p. 400 - 408

  摘要：

  DOI：

文献信息

• 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。
• Communication: Chemoselective Glycosylation Based on Difference in the Reactivities of Ethyl and <i>p</i>-Tolyl Thioglycosides
  作者：Ambar Kumar Choudhury、Indrani Mukherjee、Balaram Mukhopadhyay、Nirmolendu Roy

  DOI：10.1080/07328309908544001

  日期：1999.1.1

  Thioglycosides are very useful glycosyl donors for the synthesis of oligosaccharides.1 Frequent use of these donors is due to their ease of preparation, stability and capability of reaction in the presence of a variety of promoters like iodonium dicollidine perchlorate,2 N-iodosuccinimide–triflic acid (NIS-TfOH),3 dimethyl-(methylthio)sulfonium triflate,4 methyl triflate,5 etc. to form glycosidic bonds

  硫代糖苷是用于合成寡糖的非常有用的糖基供体。1这些供体的频繁使用是由于它们易于制备，稳定性和在各种促进剂（如高碘酸二collidine二氯吡啶，2 N-碘代琥珀酰亚胺三氟乙酸）存在下的反应能力。酸（NIS-TfOH），3-二甲基-（甲硫基）tri三氟甲磺酸酯，4-三氟甲磺酸甲酯，5等形成糖苷键。此外，武装-解除武装的糖基化策略6也已成功应用，据称2-O-取代基在激活或失活供体分子中起着更大的作用。因此，具有2-O-苄基取代基的乙基硫代糖苷供体与具有2-O-酰基保护基的乙基硫代糖苷受体的偶联以高的化学选择性进行，从而以良好的收率得到所需的产物。2，3还报道了由异头中心的激活或失活引起的活性和潜在硫糖基供体7的概念。对乙酰氨基的增强反应性...
• Neoglycoproteins
  申请人：——

  公开号：US20020164347A1

  公开（公告）日：2002-11-07

  Polyamide conjugates comprising either (a) a xenoantigenic group; or (b) a biologically active group and a macromolecular, macro- or microscopic entity; bound to a polyamide backbone, processes for their preparation and the use of these conjugates in therapeutic compositions.

  聚酰胺共轭物包含(a)异种抗原基团；或(b)生物活性基团和大分子、宏观或微观实体；结合在聚酰胺骨架上，其制备过程以及在治疗组合物中使用这些共轭物的方法。
• A Novel and Efficient Synthesis of a Dimeric Le^x Oligosaccharide on Polymeric Support
  作者：Tong Zhu、Geert-Jan Boons

  DOI：10.1021/ja001930l

  日期：2000.10.1
• Synthesis of a spacer-armed disulfated tetrasaccharide of SB1a, a carbohydrate hapten associated with human hepatocellular carcinoma
  作者：Qin Li、Hui Li、Qing Li、Qing-Hua Lou、Bin Su、Meng-Shen Cai、Zhong-Jun Li

  DOI：10.1016/s0008-6215(02)00291-4

  日期：2002.11

  A disulfated tetrasaccharide fragment with a spacer arm of human hepatocellular carcinoma carbohydrate antigen SB1a, namely, 2-aminoethyl 3-O-sulfo-beta-D-galactopyranosyl-(1 --> 3)-2-acetamido-2-deoxy-beta-D-galactopyranosyl-(1 --> 4)-3-O-sulfo-beta-D-galactopyranosyl-(1 --> 4)-beta-D-glucopyranoside was synthesized via a [2 + 1 + 1] block building mode. In the last coupling step toward the trisaccharide acceptor 8, benzoyl protected galactosyl bromide donor 14 was found to be much more reactive than the acetyl-protected donors. (C) 2002 Elsevier Science Ltd. All rights reserved.