(2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-di-O-benzyl-1-thio-β-D-glucopyranoside | 1444827-16-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-di-O-benzyl-1-thio-β-D-glucopyranoside
• 英文别名: (2-Methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-di-O-benzyl-1-thio-beta-D-glucopyranoside；[(2S,3R,4S,5S,6R)-2-(5-tert-butyl-2-methylphenyl)sulfanyl-4-hydroxy-5-phenylmethoxy-6-(phenylmethoxymethyl)oxan-3-yl] benzoate
• CAS: 1444827-16-0
• 化学式: C₃₈H₄₂O₆S
• 分子量: 626.814
• InChiKey: SORKZDYCRLJFFI-VVTWWCKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  45
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  99.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  氯甲酸-9-芴基甲酯 、 (2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-di-O-benzyl-1-thio-β-D-glucopyranoside 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以96%的产率得到(2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-di-O-benzyl-3-O-fluorenylmethoxycarbonyl-1-thio-β-D-glucopyranoside
  参考文献：
  名称：

  自动化聚糖装配产生的混合链葡聚糖低聚糖用作确定地衣酶底物特异性的工具

  摘要：

  混合键（1→3），（1→4） - d -葡聚糖（MLG）特定糖基水解地衣多糖酶是用于MLGs的结构表征一个重要的生化工具。它具有在啤酒，动物饲料和生物燃料行业中应用的潜力。通过自动聚糖组装获得的几种确定的MLG寡糖用于分析枯草芽孢杆菌的底物特异性地衣酶。两个葡萄糖构件（BBs）在C-3或C-4位置配备了一个临时的芴基甲氧基羰基氯（Fmoc）保护基，用于通过使用自动化的寡糖合成器组装不同的寡糖。光诱导从固体支持物中裂解聚糖产物，然后进行整体脱保护，提供了7种不同长度和连接性的MLG寡糖。将MLG寡糖与地衣酶一起孵育后，通过HPLC-MS分析消化产物。这些消化实验提供了对酶活性位点的见解，这与最近的其他证据一致，表明必须重新考虑地衣酶的底物特异性。

  DOI：

  10.1002/chem.201605479
• 作为产物：
  描述：

  5-叔丁基-2-甲基苯硫酚 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 硼烷四氢呋喃络合物 、 三氟甲磺酸三甲基硅酯 、 camphor-10-sulfonic acid 、 三氟化硼乙醚 、 四丁基氟化铵 、 sodium methylate 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 95.0h， 生成 (2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-di-O-benzyl-1-thio-β-D-glucopyranoside
  参考文献：
  名称：

  [EN] OLIGOSACCHARIDES AND OLIGOSACCHARIDE-PROTEIN CONJUGATES DERIVED FROM CLOSTRIDIUM DIFFICILE POLYSACCARIDE PS-I, METHODS OF SYNTHESIS AND USES THEREOF, IN PARTICULAR AS VACCINES AND DIAGNOSTIC TOOLS
  [FR] OLIGOSACCHARIDES ET CONJUGUÉS D'OLIGOSACCHARIDES-PROTÉINES PROVENANT DE POLYSACCARIDES PS-I DE CLOSTRIDIUM DIFFICILE, LEURS PROCÉDÉS DE SYNTHÈSE ET D'UTILISATION, EN PARTICULIER EN TANT QUE VACCINS ET OUTILS DE DIAGNOSTIC

  摘要：

  该发明涉及一种合成的寡糖，代表Clostridium difficile糖聚合物PS-I的重复单元的一部分，并具有五糖基序列a-L-Rhap-（1→3）-β-D-Glcp-（1→4）-[a-L-Rhap-（1→3]-a-D-Glcp-（1→2）-a-D-Glcp或其合成片段或衍生物。优选，所述的合成寡糖至少带有一个连接子L，用于与载体蛋白共轭或固定在表面上。该发明的进一步方面涉及有利的合成所述合成寡糖和寡糖-蛋白共轭的方法，以及它们的用途，特别是作为疫苗和诊断工具。

  公开号：

  WO2013017254A1

文献信息

• Automated glycan assembly of branched β-(1,3)-glucans to identify antibody epitopes
  作者：M. W. Weishaupt、H. S. Hahm、A. Geissner、P. H. Seeberger

  DOI：10.1039/c7cc00520b

  日期：——

  [small beta]-(1,3)-Glucans exhibit immunomodulatory and anti-tumor effects. Since the isolation of pure [small beta]-(1,3)-glucan oligosaccharides from natural sources is complicated, especially when certain branching patterns are desired, chemical synthesis is frequently the...

  小β-（1,3）-葡聚糖表现出免疫调节和抗肿瘤作用。由于从自然来源中分离纯的小β-（1,3）-葡聚糖寡糖非常复杂，尤其是当需要某些分支模式时，化学合成通常是...
• Gold(I)-promoted synthesis of a β-(1,3)-glucan hexadecasaccharide via the highly convergent strategy
  作者：Zixuan Wang、Qingting Hua、You Yang

  DOI：10.1016/j.carres.2019.06.014

  日期：2019.8

  gold(I)-promoted approach for the efficient assembly of a β-(1,3)-glucan hexadecasaccharide via the orthogonal and consecutive activation of thioglycosides and glucosyl ortho-hexynylbenzoates in a highly convergent manner. The synthetic hexadecasaccharide serves as the basis for further evaluation of their biological functions.

  由于难以从天然来源中分离出β-（1,3）-葡聚糖多糖，因此难以阐明β-（1,3）-葡聚糖的构效关系。我们描述了一种金（I）促进的方法，通过硫糖苷和葡糖基邻己基苯甲酸酯以高度收敛的方式进行正交和连续激活，可有效组装β-（1,3）-葡聚糖十六烷基糖。合成的十六糖用作进一步评估其生物学功能的基础。
• OLIGOSACCHARIDES AND OLIGOSACCHARIDE-PROTEIN CONJUGATES DERIVED FROM CLOSTRIDIUM DIFFICLE POLYSACCARIDE PS-I, METHODS OF SYNTHESIS AND USES THEREOF, IN PARTICULAR AS VACCINES AND DIAGNOSTIC TOOLS
  申请人：Seeberger Peter H.

  公开号：US20140193416A1

  公开（公告）日：2014-07-10

  The invention relates to a synthetic oligosaccharide representing part of the repeating unit of the Clostridium difficile glycopolymer PS-I and having the sequence of the pentasaccharide a-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[a-L-Rhap-(1→3]-a-D-Glcp-(1→2)-a-D-Glcp or a synthetic fragment or derivative thereof. Preferably, the claimed synthetic oligosaccharide bears at least one linker L for conjugation to a carrier protein or for immobilization on a surface. Further aspects of the invention relate to advantageous methods for synthesizing said synthetic oligosaccharide and oligosaccharide-protein conjugate as well as to uses thereof, in particular as vaccines and diagnostic tools.

  本发明涉及一种合成寡糖，其代表Clostridium difficile糖聚合物PS-I重复单元的一部分，并具有五糖核苷酸序列a-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[a-L-Rhap-(1→3]-a-D-Glcp-(1→2)-a-D-Glcp或其合成片段或衍生物。优选地，所述合成寡糖至少带有一种连接物L，用于与载体蛋白质结合或固定在表面上。本发明的其他方面涉及有利的方法，用于合成所述合成寡糖和寡糖-蛋白质结合物，以及其用途，特别是作为疫苗和诊断工具。
• Oligosaccharides and oligosaccharide-protein conjugates derived from Clostridium difficile polysaccharide PS-I, methods of synthesis and uses thereof, in particular as vaccines and diagnostic tools
  申请人：Seeberger Peter H.

  公开号：US09238669B2

  公开（公告）日：2016-01-19

  The invention relates to a synthetic oligosaccharide representing part of the repeating unit of the Clostridium difficile glycopolymer PS-I and having the sequence of the pentasaccharide a-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[a-L-Rhap-(1→3]-a-D-Glcp-(1→2)-a-D-Glcp or a synthetic fragment or derivative thereof. Preferably, the claimed synthetic oligosaccharide bears at least one linker L for conjugation to a carrier protein or for immobilization on a surface. Further aspects of the invention relate to advantageous methods for synthesizing said synthetic oligosaccharide and oligosaccharide-protein conjugate as well as to uses thereof, in particular as vaccines and diagnostic tools.

  本发明涉及一种合成寡糖，它代表Clostridium difficile糖聚合物PS-I重复单元的一部分，并具有五糖的序列a-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[a-L-Rhap-(1→3]-a-D-Glcp-(1→2)-a-D-Glcp或其合成片段或衍生物。优选地，所述合成寡糖至少带有一种连接物L，用于与载体蛋白质结合或固定在表面上。本发明的其他方面涉及有利的方法，用于合成所述合成寡糖和寡糖-蛋白质结合物，以及它们的用途，特别是作为疫苗和诊断工具。
• Immunological Evaluation of a Synthetic Clostridium difficile Oligosaccharide Conjugate Vaccine Candidate and Identification of a Minimal Epitope
  作者：Christopher E. Martin、Felix Broecker、Matthias A. Oberli、Julia Komor、Jochen Mattner、Chakkumkal Anish、Peter H. Seeberger

  DOI：10.1021/ja401410y

  日期：2013.7.3

  Clostridium difficile is the cause of emerging nosocomial infections that result in abundant morbidity and mortality worldwide. Thus, the development of a vaccine to kill the bacteria to prevent this disease is highly desirable. Several recently identified bacterial surface glycans, such as PS-I and PS-II, are promising vaccine candidates to preclude C difficile infection. To circumvent difficulties with the generation of natural PS-I due to its low expression levels in bacterial cultures, improved chemical synthesis protocols for the pentasaccharide repeating unit of PS-I and oligosactharide substructures were utilized to produce large quantities of well-defined PS-I related glycans. The analysis of stool and serum samples obtained from C. difficile patients using glycan microarrays of synthetic oligosaccharide epitopes revealed humoral immune responses to the PS-I related glycan epitopes. Two different vaccine candidates were evaluated in the mouse model. A synthetic PS-I repeating unit CRM197 conjugate was immunogenic in mice and induced immunoglobulin class switching as well as affinity maturation. Microarray screening employing PS-I repeating unit substructures revealed the disaccharide Rha-(1 -> 3)-Glc as a minimal epitope. A CRM197-Rha-(1 -> 3)-Glc disaccharide conjugate was able to elicit antibodies recognizing the C. difficile PS-I pentasaccharide. We herein demonstrate that glycan microarrays exposing defined oligosaccharide epitopes help to determine the minimal immunogenic epitopes of complex oligosaccharide antigens. The synthetic PS-I pentasaccharide repeating unit as well as the Rha-(1 -> 3)-Glc disaccharide are promising novel vaccine candidates against C difficile that are currently in preclinical evaluation.