diethyl 2-hydroxy-1-phenylethylphosphonate | 62573-88-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: diethyl 2-hydroxy-1-phenylethylphosphonate
• 英文别名: 2-Phenyl-2-diaethoxyphosphoryl-aethanol；Diethyl (2-hydroxy-1-phenylethyl)phosphonate；2-diethoxyphosphoryl-2-phenylethanol
• CAS: 62573-88-0
• 化学式: C₁₂H₁₉O₄P
• 分子量: 258.254
• InChiKey: GDLHTVLBHZBISB-UHFFFAOYSA-N

物化性质

• 沸点：
  381.5±35.0 °C(Predicted)
• 密度：
  1.155±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diethyl 2-hydroxy-1-phenylethylphosphonate 在 四氯化碳 、 三苯基膦 作用下， 反应 1.0h， 以50%的产率得到diethyl (2-chloro-1-phenylethyl)phosphonate
  参考文献：
  名称：

  Novel Irreversible Butyrylcholinesterase Inhibitors: 2-Chloro-1-(substituted-phenyl)ethylphosphonic Acids

  摘要：

  2-Chloroethylphosphonic acid (ethephon) as the dianion phosphorylates butyrylcholinesterase (BChE) at its active site. In contrast, the classical organophosphorus esterase inhibitors include substituted-phenyl dialkylphosphates (e.g., paraoxon) with electron-withdrawing aryl substituents. The chloroethyl and substituted-phenyl moieties are combined in this study as 2-chloro-1-(substituted-phenyl)ethylphosphonic acids (1) to define the structure-activity relationships and mechanism of BChE inhibition by ethephon and its analogues. Phenyl substituents considered are 3- and 4-nitro, 3- and 4-dimethylamino. and 3- and 4-trimethyl-ammonium. Phosphonic acids 1 were synthesized via the corresponding O,O-diethyl phosphonate precursors followed by deprotection with trimethylsilyl bromide. They decompose under basic conditions about 100-fold faster than ethephon to yield the corresponding styrene derivatives. Electron-withdrawing substituents on the phenyl ring decrease the hydrolysis rate while electron-donating substituents increase the rate. The 4-trimethylammonium analogue has the highest affinity (K-i = 180 muM) and potency (IC50 = 19 muM) in first binding reversibly at the substrate site (possibly with stabilization in a dianion-monoanion environment) and then progressively and irreversibly inhibiting the enzyme activity. These observations suggest dissociation of chloride as the first and rate-limiting step both in the hydrolysis and by analogy in phosphorylation of BChE by 1 bound at the active site. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00391-1
• 作为产物：
  描述：

  聚合甲醛 、 苯基膦酸二乙酯 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.5h， 以76%的产率得到diethyl 2-hydroxy-1-phenylethylphosphonate
  参考文献：
  名称：

  Novel Irreversible Butyrylcholinesterase Inhibitors: 2-Chloro-1-(substituted-phenyl)ethylphosphonic Acids

  摘要：

  2-Chloroethylphosphonic acid (ethephon) as the dianion phosphorylates butyrylcholinesterase (BChE) at its active site. In contrast, the classical organophosphorus esterase inhibitors include substituted-phenyl dialkylphosphates (e.g., paraoxon) with electron-withdrawing aryl substituents. The chloroethyl and substituted-phenyl moieties are combined in this study as 2-chloro-1-(substituted-phenyl)ethylphosphonic acids (1) to define the structure-activity relationships and mechanism of BChE inhibition by ethephon and its analogues. Phenyl substituents considered are 3- and 4-nitro, 3- and 4-dimethylamino. and 3- and 4-trimethyl-ammonium. Phosphonic acids 1 were synthesized via the corresponding O,O-diethyl phosphonate precursors followed by deprotection with trimethylsilyl bromide. They decompose under basic conditions about 100-fold faster than ethephon to yield the corresponding styrene derivatives. Electron-withdrawing substituents on the phenyl ring decrease the hydrolysis rate while electron-donating substituents increase the rate. The 4-trimethylammonium analogue has the highest affinity (K-i = 180 muM) and potency (IC50 = 19 muM) in first binding reversibly at the substrate site (possibly with stabilization in a dianion-monoanion environment) and then progressively and irreversibly inhibiting the enzyme activity. These observations suggest dissociation of chloride as the first and rate-limiting step both in the hydrolysis and by analogy in phosphorylation of BChE by 1 bound at the active site. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00391-1

文献信息

• YAMASHITA MITSUJI; KOJIMA MITSUMASA; YOSHIDA HIROSHI; OGATA TSUYOSHI; INO+, BULL. CHEM. SOC. JAP., 1980, 53, NO 6, 1625-1628
  作者：YAMASHITA MITSUJI、 KOJIMA MITSUMASA、 YOSHIDA HIROSHI、 OGATA TSUYOSHI、 INO+

  DOI：——

  日期：——
• Novel Irreversible Butyrylcholinesterase Inhibitors: 2-Chloro-1-(substituted-phenyl)ethylphosphonic Acids
  作者：Nanjing Zhang、John E Casida

  DOI：10.1016/s0968-0896(01)00391-1

  日期：2002.5

  2-Chloroethylphosphonic acid (ethephon) as the dianion phosphorylates butyrylcholinesterase (BChE) at its active site. In contrast, the classical organophosphorus esterase inhibitors include substituted-phenyl dialkylphosphates (e.g., paraoxon) with electron-withdrawing aryl substituents. The chloroethyl and substituted-phenyl moieties are combined in this study as 2-chloro-1-(substituted-phenyl)ethylphosphonic acids (1) to define the structure-activity relationships and mechanism of BChE inhibition by ethephon and its analogues. Phenyl substituents considered are 3- and 4-nitro, 3- and 4-dimethylamino. and 3- and 4-trimethyl-ammonium. Phosphonic acids 1 were synthesized via the corresponding O,O-diethyl phosphonate precursors followed by deprotection with trimethylsilyl bromide. They decompose under basic conditions about 100-fold faster than ethephon to yield the corresponding styrene derivatives. Electron-withdrawing substituents on the phenyl ring decrease the hydrolysis rate while electron-donating substituents increase the rate. The 4-trimethylammonium analogue has the highest affinity (K-i = 180 muM) and potency (IC50 = 19 muM) in first binding reversibly at the substrate site (possibly with stabilization in a dianion-monoanion environment) and then progressively and irreversibly inhibiting the enzyme activity. These observations suggest dissociation of chloride as the first and rate-limiting step both in the hydrolysis and by analogy in phosphorylation of BChE by 1 bound at the active site. (C) 2002 Elsevier Science Ltd. All rights reserved.