2,3,7-tri-O-acetyl-4-O-para-bromobenzyl-6-O-benzyl-L-glycero-D-manno-heptopyranosyl N-phenyltrifluoroacetimidate | 1429492-55-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,3,7-tri-O-acetyl-4-O-para-bromobenzyl-6-O-benzyl-L-glycero-D-manno-heptopyranosyl N-phenyltrifluoroacetimidate
• CAS: 1429492-55-6
• 化学式: C₃₅H₃₅BrF₃NO₁₀
• 分子量: 766.563
• InChiKey: FEQVHEYISLXNHH-HZIQQCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.38
• 重原子数：
  50.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  128.18
• 氢给体数：
  0.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  5-tert-butyl-2-methylphenyl 3,7-di-O-benzoyl-4-O-para-bromobenzyl-6-O-benzyl-1-thio-L-glycero-D-manno-heptopyranoside 、 2,3,7-tri-O-acetyl-4-O-para-bromobenzyl-6-O-benzyl-L-glycero-D-manno-heptopyranosyl N-phenyltrifluoroacetimidate 在 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以67%的产率得到
  参考文献：
  名称：

  Diversity-oriented Synthesis of Inner Core Oligosaccharides of the Lipopolysaccharide of Pathogenic Gram-negative Bacteria

  摘要：

  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.

  DOI：

  10.1021/ja401164s
• 作为产物：
  描述：

  在 吡啶 、 氨 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 反应 1.0h， 生成 2,3,7-tri-O-acetyl-4-O-para-bromobenzyl-6-O-benzyl-L-glycero-D-manno-heptopyranosyl N-phenyltrifluoroacetimidate
  参考文献：
  名称：

  Diversity-oriented Synthesis of Inner Core Oligosaccharides of the Lipopolysaccharide of Pathogenic Gram-negative Bacteria

  摘要：

  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.

  DOI：

  10.1021/ja401164s

文献信息

• Antigenic Potential of a Highly Conserved Neisseria meningitidis Lipopolysaccharide Inner Core Structure Defined by Chemical Synthesis
  作者：Anika Reinhardt、You Yang、Heike Claus、Claney L. Pereira、Andrew D. Cox、Ulrich Vogel、Chakkumkal Anish、Peter H. Seeberger

  DOI：10.1016/j.chembiol.2014.11.016

  日期：2015.1

  Neisseria meningitidis is a leading cause of bacterial meningitis worldwide. We studied the potential of synthetic lipopolysaccharide (LPS) inner core structures as broadly protective antigens against N. meningitidis. Based on the specific reactivity of human serum antibodies to synthetic LPS cores, we selected a highly conserved LPS core tetrasaccharide as a promising antigen. This LPS inner core tetrasaccharide induced a robust IgG response in mice when formulated as an immunogenic glycoconjugate. Binding of raised mouse serum to a broad collection of N. meningitidis strains demonstrated the accessibility of the LPS core on viable bacteria. The distal trisaccharide was identified as the crucial epitope, whereas the proximal Kdo moiety was immunodominant and induced mainly nonprotective antibodies that are responsible for lack of functional protection in polyclonal serum. Our results identified key antigenic determinants of LPS core glycan and, hence, may aid the design of a broadly protective immunization against N. meningitidis.