4-acetylphenyl isopropyl (S)-methylphosphonate | 948997-12-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-acetylphenyl isopropyl (S)-methylphosphonate
• CAS: 948997-12-4
• 化学式: C₁₂H₁₇O₄P
• 分子量: 256.238
• InChiKey: GKFCGMALDISXLG-KRWDZBQOSA-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 (S)-methylphosphonate 在 QFRN mutant of phosphotriesterase 作用下， 以 CHES buffer 为溶剂， 生成 对羟基苯乙酮
  参考文献：
  名称：

  国土防御酶：优化磷酸三酯酶水解有机磷神经毒剂

  摘要：

  来自土壤细菌的磷酸三酯酶 (PTE) 以其催化有机磷农药和化学战剂解毒的能力而闻名。大多数有机磷化学战剂是磷中心的两种立体异构体的混合物，S P-对映体的毒性明显高于R P-对映体。在以前的调查，PTE变体通过所述基板结合口袋的操作创建的，并显示出这些突变体具有用于解毒更大催化活性的毒性更大小号P -对映体为GB，GD，GF，VX神经剂类似物，和 VR 比毒性较小的R P- 对映异构体。在这项研究中，采用替代策略来发现其他 PTE 变体，相对于野生型酶，催化活性显着提高。筛选和选择技术用于从随机文库和位点特定修饰中分离 PTE 变体。这些新发现的 PTE 变体对S P的催化活性与野生型酶相比，GB、GD、GF、VX 和 VR 的发色类似物的对映异构体已提高了 15000 倍。确定了最佳 PTE 变体的 X 射线晶体结构。用真正的 G 型神经毒剂对这些突变体的表征证实了对 GB、GD 和 GF

  DOI：

  10.1021/bi300811t
• 作为产物：
  描述：

  对羟基苯乙酮 在 正丁基锂 、 phosphotriesterase mutant G₆₀A 作用下， 以 甲醇 、 乙醚 、 水 为溶剂， 反应 12.16h， 生成 4-acetylphenyl isopropyl (S)-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