methyl (N-benzylbenzyloxycarbonyl-5-aminopentyl 4,5,7,8-tetra-O-acetyl-3-deoxy-α-D-manno-oct-2-ulopyranosid)onate | 1403362-13-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl (N-benzylbenzyloxycarbonyl-5-aminopentyl 4,5,7,8-tetra-O-acetyl-3-deoxy-α-D-manno-oct-2-ulopyranosid)onate
• CAS: 1403362-13-9
• 化学式: C₃₇H₄₇NO₁₄
• 分子量: 729.778
• InChiKey: DGRQXVOVZPXUPV-LEWWELECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.03
• 重原子数：
  52.0
• 可旋转键数：
  18.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  179.5
• 氢给体数：
  0.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  methyl (N-benzylbenzyloxycarbonyl-5-aminopentyl 4,5,7,8-tetra-O-acetyl-3-deoxy-α-D-manno-oct-2-ulopyranosid)onate 在 palladium on activated charcoal 、 氢气 、 溶剂黄146 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 140.0h， 生成 2-(5-amino)pentyl-3-deoxy-α-D-manno-oct-2-ulopyranosidonic acid
  参考文献：
  名称：

  [EN] TOTAL SYNTHESIS AND IMMUNOLOGICAL EVALUATION OF SACCHARIDE MOIETIES OF THE LIPOPOLYSACCHARIDE FROM NEISSERIA MENINGITIDIS
  [FR] SYNTHÈSE TOTALE ET ÉVALUATION IMMUNOLOGIQUE DE FRACTIONS SACCHARIDIQUES DU LIPOPOLYSACCHARIDE PROVENANT DE NEISSERIA MENINGITIDIS

  摘要：

  本发明涉及以下通式的单糖35＃（R'=H）、双糖36＃（R'≠H；R''=H）、三糖37＃（R'≠H；R''≠H；R'''=H）和四糖1＃（R'≠H；R''≠H；R'''≠H）的全合成，其中R代表-Y-NH2，Y代表连接剂，R'为H或R''为H或R'''为H或来自脑膜炎奈瑟氏菌的脂多糖。本发明还涉及三糖37＃和四糖1＃，包含至少一个糖1＃、35＃、36＃和37＃的疫苗以及使用这种疫苗用于预防由感染四糖α-GlcNAc-(1→2)-α-Hep-(1→3)-α-Hep-(1→5)-α-Kdo或三糖α-Hep-(1→3)-α-Hep-(1→5)-α-Kdo或α-GlcNAc-(1→2)-α-Hep-(1→3)-α-Hep的细菌引起的疾病，特别是预防由脑膜炎奈瑟氏菌引起的脑膜炎、败血症、肺炎和鼻咽炎。

  公开号：

  WO2013041732A1
• 作为产物：
  描述：

  (2R,3S,4S,6S)-6-((5-(benzyl((benzyloxy)carbonyl)amino)pentyl)oxy)-2-((R)-1,2-diacetoxyethyl)-6-(methoxycarbonyl)-5-(phenylselanyl)tetrahydro-2H-pyran-3,4-diyl diacetate 在 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲苯 为溶剂， 反应 1.5h， 以94%的产率得到methyl (N-benzylbenzyloxycarbonyl-5-aminopentyl 4,5,7,8-tetra-O-acetyl-3-deoxy-α-D-manno-oct-2-ulopyranosid)onate
  参考文献：
  名称：

  [EN] TOTAL SYNTHESIS AND IMMUNOLOGICAL EVALUATION OF SACCHARIDE MOIETIES OF THE LIPOPOLYSACCHARIDE FROM NEISSERIA MENINGITIDIS
  [FR] SYNTHÈSE TOTALE ET ÉVALUATION IMMUNOLOGIQUE DE FRACTIONS SACCHARIDIQUES DU LIPOPOLYSACCHARIDE PROVENANT DE NEISSERIA MENINGITIDIS

  摘要：

  本发明涉及以下通式的单糖35＃（R'=H）、双糖36＃（R'≠H；R''=H）、三糖37＃（R'≠H；R''≠H；R'''=H）和四糖1＃（R'≠H；R''≠H；R'''≠H）的全合成，其中R代表-Y-NH2，Y代表连接剂，R'为H或R''为H或R'''为H或来自脑膜炎奈瑟氏菌的脂多糖。本发明还涉及三糖37＃和四糖1＃，包含至少一个糖1＃、35＃、36＃和37＃的疫苗以及使用这种疫苗用于预防由感染四糖α-GlcNAc-(1→2)-α-Hep-(1→3)-α-Hep-(1→5)-α-Kdo或三糖α-Hep-(1→3)-α-Hep-(1→5)-α-Kdo或α-GlcNAc-(1→2)-α-Hep-(1→3)-α-Hep的细菌引起的疾病，特别是预防由脑膜炎奈瑟氏菌引起的脑膜炎、败血症、肺炎和鼻咽炎。

  公开号：

  WO2013041732A1

文献信息

• Total synthesis of the core tetrasaccharide of the lipopolysaccharide from Neisseria meningitidis
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2573100A1

  公开（公告）日：2013-03-27

  The present invention relates to the total synthesis of the α-GlcNAc-(1→2)-α-Hep-(1→3)-α-Hep-(1→5)-α-Kdo core tetrasaccharide of the lipopolysaccharide from Neisseria meningitidis, the resulting product obtained by the total synthesis and α-GlcNAc-(1→2)-α-Hep-(1→3)-α-Hep-(1→5)-α-Kdo for use as a vaccine for immunization against diseases caused by infection with bacteria containing the tetrasaccharide, especially for immunization against meningitis, septicaemia, pneumonia and nasopharyngitis caused by Neisseria meningitidis.

  本发明涉及从脑膜炎奈瑟氏菌的脂多糖中全合成α-GlcNAc-(1→2)-α-Hep-(1→3)-α-Hep-(1→5)-α-Kdo核心四糖，所得的产物以及α-GlcNAc-(1→2)-α-Hep-(1→3)-α-Hep-(1→5)-α-Kdo用作疫苗，用于预防由含有四糖的细菌感染引起的疾病，特别是用于预防由脑膜炎奈瑟氏菌引起的脑膜炎、败血症、肺炎和鼻咽炎的免疫。
• Diversity-oriented Synthesis of Inner Core Oligosaccharides of the Lipopolysaccharide of Pathogenic Gram-negative Bacteria
  作者：You Yang、Shunsuke Oishi、Christopher E. Martin、Peter H. Seeberger

  DOI：10.1021/ja401164s

  日期：2013.4.24

  Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To better understand the role of L,PS in host-pathogen interactions and to elucidate the antigenic and immunogenic properties of LPS inner core region, a collection of well-defined L-glycero-D-manno-heptose (Hep) and 3-deoxy-alpha-D-manno-oct-2-ulosonic acid (Kdo)-containing inner core oligosaccharides is required. To address this need, we developed a diversity-oriented approach based on a common orthogonal protected disaccharide Hep-Kdo. Utilizing this new approach, we synthesized a range of LPS inner core oligosaccharides from a variety of pathogenic bacteria including Y. pestis, H. influenzae, and Proteus that cause plague, meningitis, and severe wound infections, respectively. Rapid access to these highly branched core oligosaccharides relied on elaboration of the disaccharide Hep-Kdo core as basis for the elongation with various flexible modules including unique Hep and 4-amino-4-deoxy-beta-L-arabinose (Ara4N) monosaccharides and branched Hep-Hep disaccharides. A regio- and stereoselective glycosylation of Kdo 7,8-diol was key to selective installation of the Ara4N moiety at the 8-hydroxyl group of Kdo moiety of the Hep-Kdo disaccharide. The structure of the LPS inner core oligosaccharides was confirmed by comparison of H-1 NMR spectra of synthetic antigens and isolated fragments. These synthetic LPS core oligosaccharides can be covalently bound to carrier proteins via the reducing end pentyl amine linker, to explore their antigenic and immunogenic properties as well as potential applications such as diagnostic tools and vaccines.