N-(2-hydroxyethyl)-N-{2-(tert-butyldiphenylsilyloxy)ethyl}-2,2,2-trichloroethoxymethanamide | 1428739-38-1

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: N-(2-hydroxyethyl)-N-{2-(tert-butyldiphenylsilyloxy)ethyl}-2,2,2-trichloroethoxymethanamide
• CAS: 1428739-38-1
• 化学式: C₂₃H₃₀Cl₃NO₄Si
• 分子量: 518.94
• InChiKey: SCRUFWMTEXMLFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.36
• 重原子数：
  32.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  59.0
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(2-hydroxyethyl)-N-{2-(tert-butyldiphenylsilyloxy)ethyl}-2,2,2-trichloroethoxymethanamide 在 三氟甲磺酸三甲基硅酯 、 sodium methylate 、 硝酸胍 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.5h， 生成 N-{2-(tert-butyldiphenylsilyloxy)ethyl}-N-{2-[4,6-O-benzylidene-2-deoxy-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,N-bis(2-hydroxyethyl)-2,2,2-trichloroethoxymethanamide 、 叔丁基二苯基氯硅烷 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以54%的产率得到N-(2-hydroxyethyl)-N-{2-(tert-butyldiphenylsilyloxy)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