((R)-2-hydroxy-2-((R)-2-methylenecyclopropyl)ethyl)phosphonic acid | 1564260-94-1

• 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: ((R)-2-hydroxy-2-((R)-2-methylenecyclopropyl)ethyl)phosphonic acid
• 英文别名: [(2R)-2-hydroxy-2-[(1R)-2-methylidenecyclopropyl]ethyl]phosphonic acid
• CAS: 1564260-94-1
• 化学式: C₆H₁₁O₄P
• 分子量: 178.125
• InChiKey: DSRUHUNRVQOUCP-RITPCOANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-(+)-Methylenecyclopropylmethanol 在 咪唑 、 重铬酸吡啶 、 正丁基锂 、 三甲基溴硅烷 、 四丁基氟化铵 、 烯丙基三甲基硅烷 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 39.25h， 生成 ((R)-2-hydroxy-2-((R)-2-methylenecyclopropyl)ethyl)phosphonic acid
  参考文献：
  名称：

  Mechanistic Consequences of Chiral Radical Clock Probes: Analysis of the Mononuclear Non-Heme Iron Enzyme HppE with 2-Hydroxy-3-methylenecyclopropyl Radical Clock Substrates

  摘要：

  (S)-2-Hydroxypropylphosphonic acid [(S)-HPP] epoxidase (HppE) is a mononuclear iron enzyme that catalyzes the last step in the biosynthesis of the antibiotic fosfomycin. HppE also processes the (R)enantiomer of H PP but converts it to 2-oxo-propylphosphonic acid. In this study, all four stereoisomers of 3-methylenecyclopropyl-containing substrate analogues, (2R, 3R)-8, (2R, 3S)-8, (2S, 3R)-8, and (2S, 3S)-8, were synthesized and used as radical probes to investigate the mechanism of the HppE-catalyzed reaction. Upon treatment with HppE, (2S, 3R)-8 and (2S, 3S)-8 were converted via a Cl radical intermediate to the corresponding epoxide products, as anticipated. In contrast, incubation of HppE with (2R, 3R)-8 led to enzyme inactivation, and incubation of HppE with (2R, 3S)-8 yielded the 2-keto product. The former finding is consistent with the formation of a C2 radical intermediate, where the inactivation is likely triggered by radical-induced ring cleavage of the methylenecyclopropyl group. Reaction with (2R, 3S)-8 is predicted to also proceed via a C2 radical intermediate, but no enzyme inactivation and no ring-opened product were detected. These results strongly suggest that an internal electron transfer to the iron center subsequent to C H homolysis competes with ring-opening in the processing of the C2 radical intermediate. The different outcomes of the reactions with (2R, 3R)-8 and (2R, 3S)-8 demonstrate the need to carefully consider the chirality of substituted cyclopropyl groups as radical reporting groups in studies of enzymatic mechanisms.

  DOI：

  10.1021/ja4100035

文献信息

• Mechanistic Consequences of Chiral Radical Clock Probes: Analysis of the Mononuclear Non-Heme Iron Enzyme HppE with 2-Hydroxy-3-methylenecyclopropyl Radical Clock Substrates
  作者：Hui Huang、Wei-Chen Chang、Geng-Min Lin、Anthony Romo、Pei-Jing Pai、William K. Russell、David H. Russell、Hung-Wen Liu

  DOI：10.1021/ja4100035

  日期：2014.2.26

  (S)-2-Hydroxypropylphosphonic acid [(S)-HPP] epoxidase (HppE) is a mononuclear iron enzyme that catalyzes the last step in the biosynthesis of the antibiotic fosfomycin. HppE also processes the (R)enantiomer of H PP but converts it to 2-oxo-propylphosphonic acid. In this study, all four stereoisomers of 3-methylenecyclopropyl-containing substrate analogues, (2R, 3R)-8, (2R, 3S)-8, (2S, 3R)-8, and (2S, 3S)-8, were synthesized and used as radical probes to investigate the mechanism of the HppE-catalyzed reaction. Upon treatment with HppE, (2S, 3R)-8 and (2S, 3S)-8 were converted via a Cl radical intermediate to the corresponding epoxide products, as anticipated. In contrast, incubation of HppE with (2R, 3R)-8 led to enzyme inactivation, and incubation of HppE with (2R, 3S)-8 yielded the 2-keto product. The former finding is consistent with the formation of a C2 radical intermediate, where the inactivation is likely triggered by radical-induced ring cleavage of the methylenecyclopropyl group. Reaction with (2R, 3S)-8 is predicted to also proceed via a C2 radical intermediate, but no enzyme inactivation and no ring-opened product were detected. These results strongly suggest that an internal electron transfer to the iron center subsequent to C H homolysis competes with ring-opening in the processing of the C2 radical intermediate. The different outcomes of the reactions with (2R, 3R)-8 and (2R, 3S)-8 demonstrate the need to carefully consider the chirality of substituted cyclopropyl groups as radical reporting groups in studies of enzymatic mechanisms.