(R)-di-tert-butylphosphorylglycidol | 396091-87-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: (R)-di-tert-butylphosphorylglycidol
• 英文别名: di-tert-butyl [(2R)-oxiran-2-yl]methyl phosphate；(R)-di-tert-butyl (oxiran-2-ylmethyl) phosphate；ditert-butyl [(2R)-oxiran-2-yl]methyl phosphate
• CAS: 396091-87-5
• 化学式: C₁₁H₂₃O₅P
• 分子量: 266.274
• InChiKey: QSPRALWARRVDRN-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  57.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-di-tert-butylphosphorylglycidol 在 4-二甲氨基吡啶 、 四丁基溴化铵 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 0.17h， 生成 (2S)-1-bromo-3-[(di-tert-butoxyphosphoryl)oxy]propan-2-yl (9Z)-hexadec-9-enoate
  参考文献：
  名称：

  A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA₁), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration

  摘要：

  Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA(1)) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA(1) agonists among which derivative (S)-17 (UCM-05194) stands out as the most potent and selective LPA(1) receptor agonist described so far (E-max = 118%, EC50 = 0.24 mu M, KD = 19.6 nM; inactive at autotaxin and LPA(2-6) receptors). This compound induces characteristic LPA(1)-mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.

  DOI：

  10.1021/acs.jmedchem.9b01287
• 作为产物：
  描述：

  在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.5h， 生成 (R)-di-tert-butylphosphorylglycidol
  参考文献：
  名称：

  A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA₁), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration

  摘要：

  Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA(1)) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA(1) agonists among which derivative (S)-17 (UCM-05194) stands out as the most potent and selective LPA(1) receptor agonist described so far (E-max = 118%, EC50 = 0.24 mu M, KD = 19.6 nM; inactive at autotaxin and LPA(2-6) receptors). This compound induces characteristic LPA(1)-mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.

  DOI：

  10.1021/acs.jmedchem.9b01287

文献信息

• Concise Synthesis of Glycerophospholipids
  作者：Tufan K. Mukhopadhyay、Dirk Trauner

  DOI：10.1021/acs.joc.2c02096

  日期：——

  receptors to activate biological pathways. Untangling the roles of individual glycerophospholipids requires clearly defined molecular species, a challenge that can be best addressed through chemical synthesis. However, glycerophospholipid syntheses are often lengthy due to the contrasting polarities found within these lipids. We now report a general strategy to quickly access glycerophospholipids via opening

  甘油磷脂是细胞膜的主要成分，并提供重要的信号分子。除了塑造膜特性外，有些还与特定受体结合以激活生物途径。阐明单个甘油磷脂的作用需要明确定义的分子种类，这一挑战最好通过化学合成来解决。然而，由于这些脂质中存在相反的极性，甘油磷脂的合成通常很漫长。我们现在报告了一种通过雅各布森 Co(salen) 络合物催化的羧酸与磷酸三酯环氧化物的打开来快速获得甘油磷脂的一般策略。我们表明，该方法可以应用于多种市售脂肪酸、光可切换脂肪酸和其他羧酸，以提供相应的甘油磷酸衍生物。
• Efficient Synthesis of Phospholipids from Glycidyl Phosphates
  作者：Jan Lindberg、Johan Ekeroth、Peter Konradsson

  DOI：10.1021/jo010734+

  日期：2002.1.1

  New efficient routes to enantiopure phospholipids, starting from (S)-glycidol, are described. Lysophosphatidic acids and phosphatidic acids were obtained in good overall yields from (S)-glycidol, in only three and four steps, respectively. Moreover, the strategy can also be used to produce phosphatidylcholines in three steps. Using dialkylphosphoramidites, (S)-glycidol was phosphorylated to give (R)-1-O-glycidyl dialkyl phosphates. Regiospecific epoxide opening, using hexadecanol or cesium palmitate, followed by phosphate deprotection, provided lysophosphatidic acids. 2-O-Esterification prior to phosphate deprotection provided 1,2-O-diacyl and 1-O-alkyl-2-O-acyl phosphatidic acids. Phosphorylation of (S)-glycidol using phosphorus oxychloride followed by in situ treatment with choline tosylate produced (R)-glycidyl phosphocholine. Subsequent nucleophilic opening of the epoxide using cesium palmitate produced 1-O-palmitoyl-sn-glycero-3-phosphocholine, which has been used in syntheses of phosphatidylcholines.
• Optical Control of Lysophosphatidic Acid Signaling
  作者：Johannes Morstein、Mélanie A. Dacheux、Derek D. Norman、Andrej Shemet、Prashant C. Donthamsetti、Mevlut Citir、James A. Frank、Carsten Schultz、Ehud Y. Isacoff、Abby L. Parrill、Gabor J. Tigyi、Dirk Trauner

  DOI：10.1021/jacs.0c02154

  日期：2020.6.17

  Lysophosphatidic acid (LPA) is a phospholipid that acts as an extracellular signaling molecule and activates the family of lysophosphatidic acid receptors (LPA(1-6)). These G protein-coupled receptors (GPCRs) are broadly expressed and are particularly important in development as well as in the nervous, cardiovascular, reproductive, gastrointestinal, and pulmonary systems. Here, we report on a photoswitchable analogue of LPA, termed AzoLPA, which contains an azobenzene photoswitch embedded in the acyl chain. AzoLPA enables optical control of LPA receptor activation, shown through its ability to rapidly control LPA-evoked increases in intracellular Ca2+ levels. AzoLPA shows greater activation of LPA receptors in its light-induced cis-form than its dark-adapted (or 460 nm light-induced) trans-form. AzoLPA enabled the optical control of neurite retraction through its activation of the LPA(2) receptor.
• A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA₁), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration
  作者：Inés González-Gil、Debora Zian、Henar Vázquez-Villa、Gloria Hernández-Torres、R. Fernando Martínez、Nora Khiar-Fernández、Richard Rivera、Yasuyuki Kihara、Isabel Devesa、Sakthikumar Mathivanan、Cristina Rosell del Valle、Emma Zambrana-Infantes、María Puigdomenech、Giovanni Cincilla、Melchor Sanchez-Martinez、Fernando Rodríguez de Fonseca、Antonio V. Ferrer-Montiel、Jerold Chun、Rubén López-Vales、María L. López-Rodríguez、Silvia Ortega-Gutiérrez

  DOI：10.1021/acs.jmedchem.9b01287

  日期：2020.3.12

  Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA(1)) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA(1) agonists among which derivative (S)-17 (UCM-05194) stands out as the most potent and selective LPA(1) receptor agonist described so far (E-max = 118%, EC50 = 0.24 mu M, KD = 19.6 nM; inactive at autotaxin and LPA(2-6) receptors). This compound induces characteristic LPA(1)-mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.