N-{2-(tert-butyldiphenylsilyloxy)ethyl}-N-{2-[6-O-benzyl-2-deoxy-4-O-(di-O-benzylphosphono)-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-((R)-3-tetradecanoyloxytetradecanamido)-β-D-glucopyranosyloxy]ethyl}-(R)-3-tetradecanoyloxytetradecanamide | 1428739-46-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-{2-(tert-butyldiphenylsilyloxy)ethyl}-N-{2-[6-O-benzyl-2-deoxy-4-O-(di-O-benzylphosphono)-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-((R)-3-tetradecanoyloxytetradecanamido)-β-D-glucopyranosyloxy]ethyl}-(R)-3-tetradecanoyloxytetradecanamide
• CAS: 1428739-46-1
• 化学式: C₁₃₁H₂₁₅N₂O₁₈PSi
• 分子量: 2165.21
• InChiKey: ZXHATNLAWVAQNE-PPYOQYQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  34.45
• 重原子数：
  153.0
• 可旋转键数：
  99.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  236.29
• 氢给体数：
  1.0
• 氢受体数：
  18.0

反应信息

• 作为反应物：
  描述：

  N-{2-(tert-butyldiphenylsilyloxy)ethyl}-N-{2-[6-O-benzyl-2-deoxy-4-O-(di-O-benzylphosphono)-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-((R)-3-tetradecanoyloxytetradecanamido)-β-D-glucopyranosyloxy]ethyl}-(R)-3-tetradecanoyloxytetradecanamide 在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.0h， 以90%的产率得到N-(2-hydroxyethyl)-N-{2-[6-O-benzyl-2-deoxy-4-O-(di-O-benzylphosphono)-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-((R)-3-tetradecanoyloxytetradecanamido)-β-D-glucopyranosyloxy]ethyl}-(R)-3-tetradecanoyloxytetradecanamide
  参考文献：
  名称：

  Improving the immunostimulatory potency of diethanolamine-containing lipid A mimics

  摘要：

  Lipid A is the active principal of gram negative bacterial lipopolysaccharide (LPS) in the activation of Toll-like receptor 4 (TLR4). Given the important role TLR4 plays in innate immunity and the development of adaptive immune responses, ligands that can modulate TLR4-mediated signaling have great therapeutic potential. Recently, we have reported a series of monophosphorylated lipid A mimics as potential ligands of TLR4, in which a diethanolamine moiety is employed to replace the reducing end (D-glucosamine). In this paper, we describe the synthesis of two further diethanolamine-containing lipid A mimics, 3 and 4, in an effort to mimic more closely the di-phosphate nature of natural lipid A. Both mimic 3, with an additional phosphate on the diethanolamine acyclic scaffold, and mimic 4, with a terminal carboxylic acid moiety as a phosphate bioisostere, serve to increase the potency of the immunostimulatory response induced, as measured by the induction of the cytokines TNF-alpha, IL-6, and IL-1 beta in the human monocytic cell line THP-1. In addition, mechanistic studies involving the known TLR4 antagonist lipid IVa confirm TLR4 as the target of the diethanolamine-containing lipid A mimics. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.024
• 作为产物：
  描述：

  N-{2-(tert-butyldiphenylsilyloxy)ethyl}-N-{2-[6-O-benzyl-2-deoxy-4-O-(di-O-benzylphosphono)-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-(2,2,2-trichloroethoxycarbonylamino)-β-D-glucopyranosyloxy]ethyl}-2,2,2-trichloroethoxymethanamide 、 (R)-3-(dodecanoyloxy)tetradecanoic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以381 mg的产率得到N-{2-(tert-butyldiphenylsilyloxy)ethyl}-N-{2-[6-O-benzyl-2-deoxy-4-O-(di-O-benzylphosphono)-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-((R)-3-tetradecanoyloxytetradecanamido)-β-D-glucopyranosyloxy]ethyl}-(R)-3-tetradecanoyloxytetradecanamide
  参考文献：
  名称：

  Improving the immunostimulatory potency of diethanolamine-containing lipid A mimics

  摘要：

  Lipid A is the active principal of gram negative bacterial lipopolysaccharide (LPS) in the activation of Toll-like receptor 4 (TLR4). Given the important role TLR4 plays in innate immunity and the development of adaptive immune responses, ligands that can modulate TLR4-mediated signaling have great therapeutic potential. Recently, we have reported a series of monophosphorylated lipid A mimics as potential ligands of TLR4, in which a diethanolamine moiety is employed to replace the reducing end (D-glucosamine). In this paper, we describe the synthesis of two further diethanolamine-containing lipid A mimics, 3 and 4, in an effort to mimic more closely the di-phosphate nature of natural lipid A. Both mimic 3, with an additional phosphate on the diethanolamine acyclic scaffold, and mimic 4, with a terminal carboxylic acid moiety as a phosphate bioisostere, serve to increase the potency of the immunostimulatory response induced, as measured by the induction of the cytokines TNF-alpha, IL-6, and IL-1 beta in the human monocytic cell line THP-1. In addition, mechanistic studies involving the known TLR4 antagonist lipid IVa confirm TLR4 as the target of the diethanolamine-containing lipid A mimics. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.024