(R,S)-2-Methylene-cyclopropanecarbaldehyde | 1153777-28-6

• 分子结构分类: 有机化合物 - 有机氧化合物 - 有机氧化物
• 英文名称: (R,S)-2-Methylene-cyclopropanecarbaldehyde
• 英文别名: (1R)-2-methylidenecyclopropane-1-carbaldehyde
• CAS: 1153777-28-6
• 化学式: C₅H₆O
• 分子量: 82.102
• InChiKey: RVDQZNUZKSPPND-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  6
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (R,S)-2-Methylene-cyclopropanecarbaldehyde 在 吡啶 、 咪唑 、 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 37.25h， 生成
  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
• 作为产物：
  描述：

  (R)-(+)-Methylenecyclopropylmethanol 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 生成 (R,S)-2-Methylene-cyclopropanecarbaldehyde
  参考文献：
  名称：

  (Z)- and (E)-2-(1,2-Dihydroxyethyl)methylenecyclopropane Analogues of 2′-Deoxyadenosine and 2′-Deoxyguanosine. Synthesis of All Stereoisomers, Absolute Configuration, and Antiviral Activity

  摘要：

  Chiral Z- and E-stereoisomers of (1,2-dihydroxyethyl)methylenecyclopropane analogues of 2'-deoxyadenosine and 2'-deoxyguanosine were. synthesized, and their antiviral activity was investigated. (S)-Methylenecyclo-propylcarbinol (16) was converted in seven steps to reagents 26 and 27, which were used for alkylation-elimination of adenine and 2-amino-6-chloropurine to get ultimately analogues 12a, 12b, 13a, 13b, 14a, 14b, 15a, and 15b. The enantiomeric series ent-12a, ent-12b, ent-13a, ent-13b, ent-14a, ent-14b, ent-15a, and ent-15b was obtained by similar procedures starting from (R)-methylenecyclopropylcarbinol (ent-16). The Z-isomer ent-12b was an inhibitor of two strains of human cytomegalovirus (HCMV) with EC50 of 6.8 and 7.5 mu M and of murine cytomegalovirus (MCMV) with EC50 of 11.3 mu M. It was less active against HCMV with mutated gene UL97. It inhibited Epstein-Barr virus (EBV) with EC50 of 8 mu M. The E-isomers ent-15a, ent-13a, and 15b were less effective. All adenine analogues with the exception of the Z-isomers ent-12a and ent-14a were moderate substrates for adenosine deaminase.

  DOI：

  10.1021/jm900126v