N-(benzyl)benzyloxycarbonyl-5-aminopentanyl 2,3-di-O-benzoyl-4-O-benzyl-α-L-rhamnopyranosyl-(1→3)-2-O-benzoyl-4,6-di-O-benzyl-β-D-glucopyranoside | 1444827-18-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(benzyl)benzyloxycarbonyl-5-aminopentanyl 2,3-di-O-benzoyl-4-O-benzyl-α-L-rhamnopyranosyl-(1→3)-2-O-benzoyl-4,6-di-O-benzyl-β-D-glucopyranoside
• 英文别名: N-(benzyl)benzyloxycarbonyl-5-aminopentanyl 2,3-di-O-benzoyl-4-O-benzyl-α-L-rhamnopyranosyl-(1→3)2-O-benzoyl-4,6-di-O-benzyl-1-thio-β-D-glucopyranoside
• CAS: 1444827-18-2
• 化学式: C₇₄H₇₅NO₁₅
• 分子量: 1218.41
• InChiKey: KPHFXLWCNZKKIA-SFZJRYHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.93
• 重原子数：
  90.0
• 可旋转键数：
  29.0
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  173.05
• 氢给体数：
  0.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  N-(benzyl)benzyloxycarbonyl-5-aminopentanyl 2,3-di-O-benzoyl-4-O-benzyl-α-L-rhamnopyranosyl-(1→3)-2-O-benzoyl-4,6-di-O-benzyl-β-D-glucopyranoside 在 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Immunological Evaluation of a Synthetic Clostridium difficile Oligosaccharide Conjugate Vaccine Candidate and Identification of a Minimal Epitope

  摘要：

  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.

  DOI：

  10.1021/ja401410y
• 作为产物：
  描述：

  benzyl-(5-hydroxy-pentyl)-carbamic acid benzyl ester 、 (2-methyl-5-tert-butylphenyl) 2,3-di-O-benzoyl-4-O-benzyl-α-L-rhamnopyranosyl-(1→3)-2-O-benzoyl-4,6-di-O-benzyl-1-thio-β-D-glucopyranoside 在 N-碘代丁二酰亚胺 、 三氟甲磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以91%的产率得到N-(benzyl)benzyloxycarbonyl-5-aminopentanyl 2,3-di-O-benzoyl-4-O-benzyl-α-L-rhamnopyranosyl-(1→3)-2-O-benzoyl-4,6-di-O-benzyl-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