N-{2-(tert-butyldiphenylsilyloxy)ethyl}-N-{2-[6-O-benzyl-2-deoxy-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-(2,2,2-trichloroethoxycarbonylamino)-β-D-glucopyranosyloxy]ethyl}-2,2,2-trichloroethoxymethanamide | 1428739-44-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-{2-(tert-butyldiphenylsilyloxy)ethyl}-N-{2-[6-O-benzyl-2-deoxy-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-(2,2,2-trichloroethoxycarbonylamino)-β-D-glucopyranosyloxy]ethyl}-2,2,2-trichloroethoxymethanamide
• CAS: 1428739-44-9
• 化学式: C₆₇H₁₀₀Cl₆N₂O₁₃Si
• 分子量: 1382.34
• InChiKey: WZZDIXUQDBTPDM-QQEKSEBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  15.99
• 重原子数：
  89.0
• 可旋转键数：
  43.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  177.62
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  N-{2-(tert-butyldiphenylsilyloxy)ethyl}-N-{2-[6-O-benzyl-2-deoxy-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-(2,2,2-trichloroethoxycarbonylamino)-β-D-glucopyranosyloxy]ethyl}-2,2,2-trichloroethoxymethanamide 、 二苯基N,N'-二异丙基亚磷酰胺 在 5-苯基四氮唑 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以85%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-(2,2,2-trichloroethoxycarbonylamino)-β-D-glucopyranosyloxy]ethyl}-2,2,2-trichloroethoxymethanamide
  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-hydroxyethyl)-N-{2-(tert-butyldiphenylsilyloxy)ethyl}-2,2,2-trichloroethoxymethanamide 在 盐酸 、 4-二甲氨基吡啶 、 三氟甲磺酸三甲基硅酯 、 sodium methylate 、 硝酸胍 、 sodium cyanoborohydride 、 对甲苯磺酸 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 10.5h， 生成 N-{2-(tert-butyldiphenylsilyloxy)ethyl}-N-{2-[6-O-benzyl-2-deoxy-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-(2,2,2-trichloroethoxycarbonylamino)-β-D-glucopyranosyloxy]ethyl}-2,2,2-trichloroethoxymethanamide
  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