diethyl (2-cyclopropyl-2-hydroxyethyl)phosphonate | 1400998-63-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: diethyl (2-cyclopropyl-2-hydroxyethyl)phosphonate
• CAS: 1400998-63-1
• 化学式: C₉H₁₉O₄P
• 分子量: 222.221
• InChiKey: SXKFUUIGGLDTBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.02
• 重原子数：
  14.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  55.76
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  diethyl (2-cyclopropyl-2-hydroxyethyl)phosphonate 在 吡啶 、 pig liver esterase 、 三甲基溴硅烷 、 (S)-2-hydroxypropylphosphonic acid epoxidase 、 sodium hydroxide 、 烯丙基三甲基硅烷 作用下， 以 aq. phosphate buffer 、 二氯甲烷 、 水 为溶剂， 反应 68.6h， 生成 (2-cyclopropyl-2-oxoethyl)phosphonic acid
  参考文献：
  名称：

  Evidence for Radical-Mediated Catalysis by HppE: A Study Using Cyclopropyl and Methylenecyclopropyl Substrate Analogues

  摘要：

  (S)-2-Hydroxypropylphosphonic acid epoxidase (HppE) is an unusual mononuclear iron enzyme that catalyzes the oxidative epoxidation of (S)-2-hydroxypropylphosphonic acid ((S)-HPP) in the biosynthesis of the antibiotic fosfomycin. HppE also recognizes (R)-2-hydroxypropylphosphonic acid ((R)-HPP) as a substrate and converts it to 2-oxo-propylphosphonic acid. To probe the mechanisms of these HppE-catalyzed oxidations, cyclopropyl- and methylenecyclopropyl-containing compounds were synthesized and studied as radical clock substrate analogues. Enzymatic assays indicated that the (S)- and (R)-isomers of the cyclopropyl-containing analogues were efficiently converted to epoxide and ketone products by HppE, respectively. In contrast, the ultrafast methylenecyclopropyl-containing probe inactivated HppE, consistent with a rapid radical-triggered ring-opening process that leads to enzyme inactivation. Taken together, these findings provide, for the first time, experimental evidence for the involvement of a C2-centered radical intermediate with a lifetime on the order of nanoseconds in the HppE-catalyzed oxidation of (R)-HPP.

  DOI：

  10.1021/ja3078126
• 作为产物：
  描述：

  2-溴-1-环丙基乙酮 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 13.0h， 生成 diethyl (2-cyclopropyl-2-hydroxyethyl)phosphonate
  参考文献：
  名称：

  Evidence for Radical-Mediated Catalysis by HppE: A Study Using Cyclopropyl and Methylenecyclopropyl Substrate Analogues

  摘要：

  (S)-2-Hydroxypropylphosphonic acid epoxidase (HppE) is an unusual mononuclear iron enzyme that catalyzes the oxidative epoxidation of (S)-2-hydroxypropylphosphonic acid ((S)-HPP) in the biosynthesis of the antibiotic fosfomycin. HppE also recognizes (R)-2-hydroxypropylphosphonic acid ((R)-HPP) as a substrate and converts it to 2-oxo-propylphosphonic acid. To probe the mechanisms of these HppE-catalyzed oxidations, cyclopropyl- and methylenecyclopropyl-containing compounds were synthesized and studied as radical clock substrate analogues. Enzymatic assays indicated that the (S)- and (R)-isomers of the cyclopropyl-containing analogues were efficiently converted to epoxide and ketone products by HppE, respectively. In contrast, the ultrafast methylenecyclopropyl-containing probe inactivated HppE, consistent with a rapid radical-triggered ring-opening process that leads to enzyme inactivation. Taken together, these findings provide, for the first time, experimental evidence for the involvement of a C2-centered radical intermediate with a lifetime on the order of nanoseconds in the HppE-catalyzed oxidation of (R)-HPP.

  DOI：

  10.1021/ja3078126