S-(2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-O-benzylidene-3-O-tert-butyldimethylsilyl-1-thio-β-D-glucopyranoside | 1334540-50-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: S-(2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-O-benzylidene-3-O-tert-butyldimethylsilyl-1-thio-β-D-glucopyranoside
• 英文别名: (2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-O-benzylidene-3-O-tert-butyldimethylsilyl-1-thio-β-D-glucopyranoside
• CAS: 1334540-50-9
• 化学式: C₃₇H₄₈O₆SSi
• 分子量: 648.936
• InChiKey: NLKVTWYRSIPZQI-GLPBNNEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.84
• 重原子数：
  45.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  63.22
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  S-(2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-O-benzylidene-3-O-tert-butyldimethylsilyl-1-thio-β-D-glucopyranoside 在 N-碘代丁二酰亚胺 、 copper(l) iodide 、 四(三苯基膦)钯 、 三氟甲磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 5.5h， 生成
  参考文献：
  名称：

  金（I）催化的糖基壬二酸酯作为供体的糖基化

  摘要：

  开发了一种简单且通用的糖基化方法，其中武装和解除武装的糖基炔诺酸酯都作为供体。在有或没有TfOH的辅助下采用金（I）配合物作为催化剂，本糖基化方案的范围非常宽。通过潜在的活性策略和多重正交一锅策略在低聚糖的有效合成中证明了本发明的炔酸供体的实用性。最后，该方法能够正式合成肺炎链球菌血清型3的四糖半抗原和32mer聚甘露糖苷的高度收敛合成。

  DOI：

  10.1021/acs.orglett.9b03851
• 作为产物：
  描述：

  β-D-葡萄糖五乙酸酯 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 camphor-10-sulfonic acid 、 三氟化硼乙醚 、 sodium methylate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.5h， 生成 S-(2-methyl-5-tert-butylphenyl) 2-O-benzoyl-4,6-O-benzylidene-3-O-tert-butyldimethylsilyl-1-thio-β-D-glucopyranoside
  参考文献：
  名称：

  Progress toward developing a carbohydrate-conjugate vaccine against Clostridium difficile ribotype 027: synthesis of the cell-surface polysaccharide PS-I repeating unit

  摘要：

  克劳斯特里迪姆·迪菲西尔株核糖型027是一种高度毒力病原体，导致了最近严重的医院感染暴发。作为开发基于碳水化合物的预防性疫苗的基础，我们通过对四种单糖构件进行线性组合，合成了该株特有的PS-I五糖细胞壁重复单元。

  DOI：

  10.1039/c1cc13614c

文献信息

• Automated glycan assembly of a <i>S. pneumoniae</i> serotype 3 CPS antigen
  作者：Markus W Weishaupt、Stefan Matthies、Mattan Hurevich、Claney L Pereira、Heung Sik Hahm、Peter H Seeberger

  DOI：10.3762/bjoc.12.139

  日期：——

  Vaccines against S. pneumoniae, one of the most prevalent bacterial infections causing severe disease, rely on isolated capsular polysaccharide (CPS) that are conjugated to proteins. Such isolates contain a heterogeneous oligosaccharide mixture of different chain lengths and frame shifts. Access to defined synthetic S. pneumoniae CPS structures is desirable. Known syntheses of S. pneumoniae serotype 3 CPS rely on a time-consuming and low-yielding late-stage oxidation step, or use disaccharide building blocks which limits variability. Herein, we report the first iterative automated glycan assembly (AGA) of a conjugation-ready S. pneumoniae serotype 3 CPS trisaccharide. This oligosaccharide was assembled using a novel glucuronic acid building block to circumvent the need for a late-stage oxidation. The introduction of a washing step with the activator prior to each glycosylation cycle greatly increased the yields by neutralizing any residual base from deprotection steps in the synthetic cycle. This process improvement is applicable to AGA of many other oligosaccharides.

  针对导致严重疾病的最常见细菌感染之一的肺炎球菌的疫苗依赖于与蛋白质结合的分离的胶囊多糖（CPS）。这种分离物包含不同链长和框移的异质寡糖混合物。获得定义明确的合成肺炎球菌CPS结构是可取的。已知的肺炎球菌3型CPS的合成依赖于耗时且产率低的后期氧化步骤，或者使用二糖建筑块，这限制了变异性。在这里，我们报告了第一个迭代自动糖基组装（AGA）的可结合的肺炎球菌3型CPS三糖的组装。使用一种新型葡萄糖醛酸建筑块组装了这种寡糖，以避免需要后期氧化。在每个糖基化周期之前引入一个活化剂的洗涤步骤大大增加了产量，通过中和合成周期中去保护步骤中的任何残留碱。这个工艺改进适用于许多其他寡糖的AGA。
• Oligosaccharides and oligosaccharides-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：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2554549A1

  公开（公告）日：2013-02-06

  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 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 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. A preferred method for synthesizing the pentasaccharide is shown below.

  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α-L-Rhap-(1→3)-β-D-Glcp-(1→4)-[α-L-Rhap-(1→3)]-α-D-Glcp-(1→2)-α-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体L，用于与载体蛋白结合或在表面上固定。该发明的其他方面涉及有利的合成所述合成寡糖和寡糖-蛋白共轭物的方法，以及它们的用途，特别是作为疫苗和诊断工具。下面显示了一种合成五糖基的首选方法。
• 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...
• 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.