ethyl α-diethoxyphosphoryl-α-(3-nitrophenyl)acetate | 449777-32-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl α-diethoxyphosphoryl-α-(3-nitrophenyl)acetate
• 英文别名: ethyl 2-(diethoxyphosphoryl)-2-(3-nitrophenyl)acetate；Ethyl 2-[diethoxy(oxido)phosphaniumyl]-2-(3-nitrophenyl)acetate
• CAS: 449777-32-6
• 化学式: C₁₄H₂₀NO₇P
• 分子量: 345.289
• InChiKey: YLCYHYCMNBJJNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl α-diethoxyphosphoryl-α-(3-nitrophenyl)acetate 在 palladium on activated charcoal 四氯化碳 、 硼烷 、 氢气 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 51.0h， 生成 diethyl 1-(3-aminophenyl)-2-chloroethylphosphonate
  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：

  磷酰基乙酸三乙酯 、 1-碘-3-硝基苯 在 copper(l) iodide 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以67%的产率得到ethyl α-diethoxyphosphoryl-α-(3-nitrophenyl)acetate
  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

• Route to α-Aryl Phosphonoacetates: Useful Synthetic Precursors in the Horner–Wadsworth–Emmons Olefination
  作者：Kelsey F. VanGelder、Melinda Wang、Marisa C. Kozlowski

  DOI：10.1021/acs.joc.5b01887

  日期：2015.10.16

  A versatile and general catalytic strategy has been developed for the alpha-arylation of phosphonoacetates utilizing parallel microscale experimentation. These a-substituted phosphonoacetates are widely useful, notably as substrates in the Horner-Wadsworth-Emmons-type olefinations. However, the current routes to these products involve harsh conditions, limiting the variety of functionality. The reported method can be used with a variety of aryl chlorides and aryl bromides, including several heterocyclic examples.