N-{2-phosphonoethyl}-N-{2-[2-deoxy-4-O-phosphono-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-((R)-3-tetradecanoyloxytetradecanamido)-β-D-glucopyranosyloxy]ethyl}-(R)-3-tetradecanoyloxytetradecanamide | 1428739-35-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-{2-phosphonoethyl}-N-{2-[2-deoxy-4-O-phosphono-3-O-((R)-3-tetradecanoyloxytetradecanoyl)-2-((R)-3-tetradecanoyloxytetradecanamido)-β-D-glucopyranosyloxy]ethyl}-(R)-3-tetradecanoyloxytetradecanamide
• 英文别名: [(2R,3S,4R,5R,6R)-2-(hydroxymethyl)-3-phosphonooxy-6-[2-[2-phosphonooxyethyl-[(3R)-3-tetradecanoyloxytetradecanoyl]amino]ethoxy]-5-[[(3R)-3-tetradecanoyloxytetradecanoyl]amino]oxan-4-yl] (3R)-3-tetradecanoyloxytetradecanoate
• CAS: 1428739-35-8
• 化学式: C₉₄H₁₈₀N₂O₂₁P₂
• 分子量: 1736.41
• InChiKey: GTENBFIDYWMDPV-UQSQAMLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  29.7
• 重原子数：
  119
• 可旋转键数：
  92
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  327
• 氢给体数：
  6
• 氢受体数：
  21

反应信息

• 作为产物：
  描述：

  N-{2-(di-O-benzylphosphono)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 5%-palladium/activated carbon 、 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以70%的产率得到N-{2-phosphonoethyl}-N-{2-[2-deoxy-4-O-phosphono-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

文献信息

• Improving the immunostimulatory potency of diethanolamine-containing lipid A mimics
  作者：Jordan D. Lewicky、Marina Ulanova、Zi-Hua Jiang

  DOI：10.1016/j.bmc.2013.02.024

  日期：2013.4

  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.