(2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-di-O-benzyl-3-O-tert-butyldimethylsilyl-1-thio-β-D-glucopyranoside | 1421767-99-8

• 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-3-O-tert-butyldimethylsilyl-1-thio-β-D-glucopyranoside
• 英文别名: (2-Methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-di-O-benzyl-3-O-tert-butyldimethylsilyl-1-thio-beta-D-glucopyranoside；[(2S,3R,4S,5R,6R)-4-[tert-butyl(dimethyl)silyl]oxy-2-(5-tert-butyl-2-methylphenyl)sulfanyl-5-phenylmethoxy-6-(phenylmethoxymethyl)oxan-3-yl] benzoate
• CAS: 1421767-99-8
• 化学式: C₄₄H₅₆O₆SSi
• 分子量: 741.077
• InChiKey: CQPMMRGSOLMHDE-SRDZHKAFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.53
• 重原子数：
  52
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  88.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-di-O-benzyl-3-O-tert-butyldimethylsilyl-1-thio-β-D-glucopyranoside 在 4-二甲氨基吡啶 、 N-碘代丁二酰亚胺 、 2,6-二叔丁基吡啶 、 silver trifluoromethanesulfonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 1.33h， 生成 2-O-benzoyl-4,6-di-O-benzyl-3-O-tert-butyldimethylsilyl-D-glucopyranosyl orthohexynylbenzoate
  参考文献：
  名称：

  金（I）通过高度收敛的策略促进了β-（1,3）-葡聚糖十六糖的合成

  摘要：

  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。

  DOI：

  10.1016/j.carres.2019.06.014
• 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 、 sodium methylate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 23.0h， 生成 (2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-di-O-benzyl-3-O-tert-butyldimethylsilyl-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

• 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。
• ANTIBODIES FOR PREVENTION AND TREATMENT OF DISEASES CAUSED BY CLOSTRIDIUM DIFFICILE
  申请人：Max-Planck-Gesellschaft zur Foerderung der Wissenschaften e.V.

  公开号：US20160137724A1

  公开（公告）日：2016-05-19

  The present invention relates to an antibody having specificity for an immunogenic determinant consisting of the pentasaccharide repeating unit of the Clostridium difficile glycopolymer PS-I: α- L -Rhap-(1→3)-β- D -Glcp-(1→4)-[α- L -Rhap-(1→3)]-α- D -Glcp-(1→2)-α- D -Glcp or a fragment thereof. Said antibody is able to prevent and treat diseases caused by C. difficile . The present invention further pertains to a method of treating or preventing a disease caused by the pathogen Clostridium difficile , which comprises administering to a subject said antibody or a vaccine composition comprising said antibody.

  本发明涉及一种具有特异性的抗体，其针对克罗斯特菌困难梭菌糖聚合物PS-I的五糖重复单元或其片段的免疫表位。该抗体能够预防和治疗由C. difficile引起的疾病。本发明还涉及一种治疗或预防由病原体Clostridium difficile引起的疾病的方法，该方法包括向受试者注射所述抗体或包含所述抗体的疫苗组合物。
• Stereoselective synthesis of α-glucosides with glucosyl (Z)-Ynenoates as donors
  作者：Zhi Ma、Yi Hu、Xiaona Li、Rongkun Liu、E Xia、Peng Xu、You Yang

  DOI：10.1016/j.carres.2022.108710

  日期：2023.1

  DMF-modulated glycosylation approach with glycosyl (Z)-ynenoates as donors was developed for highly α-selective synthesis of various linkage types of α-glucans. The substituent groups were also found to play a significant role in the α-selective glucosylation reactions. The glycosylation approach was effectively applied to the stereospecific synthesis of the α-1,6-linked triglucoside.

  开发了一种以糖基 ( Z )-炔诺酸酯作为供体的 SPhosAuNTf 2促进 DMF 调节的糖基化方法，用于各种连接类型的 α-葡聚糖的高 α-选择性合成。还发现取代基在α-选择性糖基化反应中起重要作用。糖基化方法有效地应用于 α-1,6-连接的三葡萄糖苷的立体特异性合成。
• 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.