4-acetylphenyl isopropyl methylphosphonate | 948997-10-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-acetylphenyl isopropyl methylphosphonate
• CAS: 948997-10-2
• 化学式: C₁₂H₁₇O₄P
• 分子量: 256.238
• InChiKey: GKFCGMALDISXLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 重原子数：
  17.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-acetylphenyl isopropyl methylphosphonate 在 phosphotriesterase mutant H₂₅₇Y/L₃₀₃T 作用下， 以 甲醇 、 水 为溶剂， 以74%的产率得到
  参考文献：
  名称：

  Stereoselective Hydrolysis of Organophosphate Nerve Agents by the Bacterial Phosphotriesterase

  摘要：

  Organophosphorus compounds include many synthetic, neurotoxic substances that are commonly used as insecticides. The toxicity of these compounds is due to their ability to inhibit the enzyme acetylcholine esterase. Some of the most toxic organophosphates have been adapted for use as chemical warfare agents; the most well-known are GA, GB, GD, GF, VX, and VR. All of these compounds contain a chiral phosphorus center, with the S-P enantiomers being significantly more toxic than the R-P enantiomers. Phosphotriesterase (PTE) is an enzyme capable of detoxifying these agents, but the stereochemical preference of the wild-type enzyme is for the R-P enantiomers. A series of enantiomerically pure chiral nerve agent analogues containing the relevant phosphoryl centers found in GB, GD, GF, VX, and VR has been developed. Wild-type and mutant forms of PTE have been tested for their ability to hydrolyze this series of compounds. Mutant forms of PTE with significantly enhanced, as well as relaxed or reversed, stereoselectivity have been identified. A number of variants exhibited dramatically improved kinetic constants for the catalytic hydrolysis of the more toxic S-P enantiomers. Improvements of up to 3 orders of magnitude relative to the value of the wild-type enzyme were observed. Some of these mutants were tested against racemic mixtures of GB and GD. The kinetic constants obtained with the chiral nerve agent analogues accurately predict the improved activity and stereoselectivity against the authentic nerve agents used in this study.

  DOI：

  10.1021/bi101056m
• 作为产物：
  描述：

  甲基膦酞二氯 、 异丙醇 、 对羟基苯乙酮 在 正丁基锂 、 三乙胺 作用下， 以 乙醚 为溶剂， 反应 12.16h， 生成 4-acetylphenyl isopropyl methylphosphonate
  参考文献：
  名称：

  Stereoselective Hydrolysis of Organophosphate Nerve Agents by the Bacterial Phosphotriesterase

  摘要：

  Organophosphorus compounds include many synthetic, neurotoxic substances that are commonly used as insecticides. The toxicity of these compounds is due to their ability to inhibit the enzyme acetylcholine esterase. Some of the most toxic organophosphates have been adapted for use as chemical warfare agents; the most well-known are GA, GB, GD, GF, VX, and VR. All of these compounds contain a chiral phosphorus center, with the S-P enantiomers being significantly more toxic than the R-P enantiomers. Phosphotriesterase (PTE) is an enzyme capable of detoxifying these agents, but the stereochemical preference of the wild-type enzyme is for the R-P enantiomers. A series of enantiomerically pure chiral nerve agent analogues containing the relevant phosphoryl centers found in GB, GD, GF, VX, and VR has been developed. Wild-type and mutant forms of PTE have been tested for their ability to hydrolyze this series of compounds. Mutant forms of PTE with significantly enhanced, as well as relaxed or reversed, stereoselectivity have been identified. A number of variants exhibited dramatically improved kinetic constants for the catalytic hydrolysis of the more toxic S-P enantiomers. Improvements of up to 3 orders of magnitude relative to the value of the wild-type enzyme were observed. Some of these mutants were tested against racemic mixtures of GB and GD. The kinetic constants obtained with the chiral nerve agent analogues accurately predict the improved activity and stereoselectivity against the authentic nerve agents used in this study.

  DOI：

  10.1021/bi101056m