(S)-diethyl (2-cyclopropyl-2-hydroxyethyl)phosphonate

• 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: (S)-diethyl (2-cyclopropyl-2-hydroxyethyl)phosphonate
• 英文别名: (1S)-1-cyclopropyl-2-[diethoxy(oxido)phosphaniumyl]ethanol
• 化学式: C₉H₁₉O₄P
• 分子量: 222.221
• InChiKey: SXKFUUIGGLDTBB-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-diethyl (2-cyclopropyl-2-hydroxyethyl)phosphonate 在 三甲基溴硅烷 、 烯丙基三甲基硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以85%的产率得到(S)-(2-cyclopropyl-2-hydroxyethyl)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 吡啶 、 sodium tetrahydroborate 、 pig liver esterase 作用下， 以 甲醇 、 aq. phosphate buffer 为溶剂， 反应 45.0h， 生成 (S)-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

文献信息

• Asymmetric hydrogenation of β-ketophosphonates and β-ketothiophosphonates with chiral ru (II) catalysts
  作者：Isabelle Gautier、Virginie Ratovelomanana-Vidal、Philippe Savignac、Jean-Pierre Genêt

  DOI：10.1016/0040-4039(96)01733-9

  日期：1996.10

  Asymmetric hydrogenation of β-ketophosphonates and β-ketothiophosphonates is described. Enantiomeric excesses up to 99% were obtained.

  描述了β-酮膦酸酯和β-酮硫代膦酸酯的不对称氢化。获得了高达99％的对映体过量。
• Enantioselective ruthenium-mediated hydrogenation: developments and applications
  作者：Virginie Ratovelomanana-Vidal、Jean-Pierre Genêt

  DOI：10.1016/s0022-328x(98)00680-9

  日期：1998.9

  A general preparation of chiral ruthenium(II) catalysts and the homogeneous enantioselective hydrogenation of prochiral olefins and keto groups are presented. Some applications to the synthesis of biologically active compounds are reported. (C) 1998 Elsevier Science S.A. All rights reserved.
• Evidence for Radical-Mediated Catalysis by HppE: A Study Using Cyclopropyl and Methylenecyclopropyl Substrate Analogues
  作者：Hui Huang、Wei-chen Chang、Pei-Jing Pai、Anthony Romo、Steven O. Mansoorabadi、David H. Russell、Hung-wen Liu

  DOI：10.1021/ja3078126

  日期：2012.10.3

  (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.