(1R,2S)-2-bromo-2-methylcyclopropanecarboxylic acid | 136171-96-5

• 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: (1R,2S)-2-bromo-2-methylcyclopropanecarboxylic acid
• 英文别名: (1R,2S)-2-bromo-2-methylcyclopropane-1-carboxylic acid
• CAS: 136171-96-5
• 化学式: C₅H₇BrO₂
• 分子量: 179.013
• InChiKey: NYZUJAVLSSPOKR-WUJLRWPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,2S)-2-bromo-2-methylcyclopropanecarboxylic acid 在 lithium aluminium deuteride 、 3 A molecular sieve 、 sodium carbonate 、 pyridinium chlorochromate 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-<(R)-1'-phenyl-2'-hydroxyethyl>-(1R,αS)-<α-(2)H>methylenecyclopropaneacetamide
  参考文献：
  名称：

  Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A

  摘要：

  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.

  DOI：

  10.1021/ja00019a040
• 作为产物：
  描述：

  2-溴-2-甲基环丙烷-1-羧酸乙酯 在 硫酸 、 水 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 56.0h， 生成 (1R,2S)-2-bromo-2-methylcyclopropanecarboxylic acid
  参考文献：
  名称：

  Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A

  摘要：

  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.

  DOI：

  10.1021/ja00019a040