ethyl trans-2-bromo-2-methylcyclopropanecarboxylate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl trans-2-bromo-2-methylcyclopropanecarboxylate
• 英文别名: ethyl (1S,2R)-2-bromo-2-methylcyclopropane-1-carboxylate
• 化学式: C₇H₁₁BrO₂
• 分子量: 207.067
• InChiKey: UGIMXAFCWYSYOZ-CAHLUQPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  重氮乙酸乙酯 、 2-溴丙烯 在 rhodium(II) acetate dimer 作用下， 以50%的产率得到ethyl trans-2-bromo-2-methylcyclopropanecarboxylate
  参考文献：
  名称：

  亚甲基环丙基甘氨酸的毒性：研究（亚甲基环丙基）甲酰辅酶 A 对参与脂肪酸代谢的酶的抑制作用及其使烯酰辅酶 A 水合酶失活的分子基础

  摘要：

  (亚甲基环丙基)甲酰基-CoA (MCPF-CoA) 是亚甲基环丙基甘氨酸 (MCPG) 的一种有毒代谢物，由于其能够中断脂肪酸代谢的 β-氧化途径，因此已知具有降血糖活性。早期的实验表明，乙酰乙酰辅酶 A 硫解酶、3-酮酰基辅酶 A 硫解酶、酰基辅酶 A 脱氢酶和烯酰辅酶 A 水合酶 (ECH) 是可被 MCPF-CoA 和/或 MCPG 抑制的细胞靶点。为了获得有关靶标特异性和作用方式的更多见解，我们对 MCPF-CoA 对参与脂肪酸代谢的各种酶的影响进行了详细研究。我们的研究证实，MCPF-CoA 是 ECH 的有效灭活剂，但对本研究中测试的其他 β-氧化酶几乎没有影响。

  DOI：

  10.1021/ja991908w

文献信息

• Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A
  作者：Ming Tain Lai、Li Da Liu、Hung Wen Liu

  DOI：10.1021/ja00019a040

  日期：1991.9

  General acyl-CoA dehydrogenase (GAD) is a flavin-dependent (FAD) enzyme that catalyzes the oxidation of a fatty acyl-CoA to the corresponding alpha,beta-enolyl-CoA. When GAD is exposed to (methylenecyclopropyl)acetyl-CoA (MCPA-CoA), a metabolite of hypoglycin A that is the causative agent of Jamaican vomiting sickness, time-dependent inhibition occurs with concomitant bleaching of the active-site FAD. The inactivation mechanism is generally believed to be initiated by C-alpha anion formation followed by ring fragmentation and the covalent modification of FAD. However, formation of a cyclopropyl radical intermediate through one-electron oxidation followed by ring opening and then radical recombination to yield a modified FAD is an appealing alternative. As described herein, studies of the inactivation of GAD by (1S)- and (1R)-MCPA-CoA bearing a stereospecific tritium label at C-alpha have provided direct evidence suggesting that C-alpha proton abstraction occurs during inactivation and the two diastereomers of MCPA-CoA bind to the same locus in the active site of GAD. Despite the fact that the inactivations mediated by (1R)- and (1S)-MCPA-CoA proceed at different rates, the observed partition ratios are almost identical. Using [alpha,alpha-H-2(2)]MCPA-CoA as inhibitors, we have found that the sluggish inactivation observed for (1S)-MCPA-CoA is not due to mechanistic rerouting, but is instead a result of the retardation of the initial deprotonation step. Thus, the equivalent partition ratios found in these studies clearly indicate that inactivation by either (1R)- or (1S)-MCPA-CoA follows the same chemical course. Such a lack of stereospecificity for the bond rupture at C-beta of MCPA-CoA in the enzyme active site suggests that the ring-opening step leading to inactivation is likely a spontaneous event. Since the rearrangement of alpha-cyclopropyl radicals to ring-opened alkyl radicals is extremely rapid, the ring cleavage induced by an alpha-cyclopropyl radical may bypass the chiral discrimination normally imposed by the enzyme. Thus, the mechanistic insights deduced from this study support our early notion that inactivation of GAD by MCPA-CoA is likely to proceed through a radical mechanism.
• The Toxicity of Methylenecyclopropylglycine:  Studies of the Inhibitory Effects of (Methylenecyclopropyl)formyl-CoA on Enzymes Involved in Fatty Acid Metabolism and the Molecular Basis of Its Inactivation of Enoyl-CoA Hydratases
  作者：Ding Li、Gautam Agnihotri、Srikanth Dakoji、Eugene Oh、Marily Lantz、Hung-wen Liu

  DOI：10.1021/ja991908w

  日期：1999.10.1

  (Methylenecyclopropyl)formyl-CoA (MCPF-CoA), a toxic metabolite of methylenecyclopropylglycine (MCPG), is known to have hypoglycemic activity due to its ability to interrupt the β-oxidation pathway of fatty acid metabolism. Earlier experiments have shown that acetoacetyl-CoA thiolase, 3-ketoacyl-CoA thiolase, acyl-CoA dehydrogenases, and enoyl-CoA hydratase (ECH) are cellular targets that can be inhibited

  (亚甲基环丙基)甲酰基-CoA (MCPF-CoA) 是亚甲基环丙基甘氨酸 (MCPG) 的一种有毒代谢物，由于其能够中断脂肪酸代谢的 β-氧化途径，因此已知具有降血糖活性。早期的实验表明，乙酰乙酰辅酶 A 硫解酶、3-酮酰基辅酶 A 硫解酶、酰基辅酶 A 脱氢酶和烯酰辅酶 A 水合酶 (ECH) 是可被 MCPF-CoA 和/或 MCPG 抑制的细胞靶点。为了获得有关靶标特异性和作用方式的更多见解，我们对 MCPF-CoA 对参与脂肪酸代谢的各种酶的影响进行了详细研究。我们的研究证实，MCPF-CoA 是 ECH 的有效灭活剂，但对本研究中测试的其他 β-氧化酶几乎没有影响。