(1R)-亚甲基环丙烷乙酸 | 125873-64-5

• 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
• 中文名称: (1R)-亚甲基环丙烷乙酸
• 中文别名: 环丙乙酸,2-亚甲基-,(R)-
• 英文名称: (1R)-methylenecyclopropaneacetic acid
• 英文别名: 2-[(1R)-2-methylidenecyclopropyl]acetic acid
• CAS: 125873-64-5
• 化学式: C₆H₈O₂
• 分子量: 112.128
• InChiKey: QJBXAEKEXKLLLZ-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 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)-亚甲基环丙烷乙酸 在 sodium hydroxide 、 三乙胺 作用下， 以 水 为溶剂， 反应 1.34h， 生成 (R)-(2-methylenecyclopropyl)acetyl-CoA
  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：

  (1R)-(Methylenecyclopropyl)acetonitrile 在 chromium(VI) oxide 、 硫酸 、 二异丁基氢化铝 作用下， 生成 (1R)-亚甲基环丙烷乙酸
  参考文献：
  名称：

  Lai, Ming-Tain; Liu, Hung-Wen, Journal of the American Chemical Society, 1990, vol. 112, # 10, p. 4034 - 4035

  摘要：

  DOI：

文献信息

• Spiropentylacetyl-CoA, A Mechanism-Based Inactivator of Acyl-CoA Dehydrogenases
  作者：Ding Li、Hui-qiang Zhou、Srikanth Dakoji、Injae Shin、Eugene Oh、Hung-wen Liu

  DOI：10.1021/ja9737634

  日期：1998.3.1

  However, recent studies of the inactivation of ACDs by a metabolite of hypoglycin A, (methylenecyclopropyl)acetyl-CoA (MCPA-CoA), led to an alternative mechanism in which the reducing equivalent is delivered from the initially formed α-anion to the bound FAD via a single electron transfer process. To further explore the observed mechanistic discrepancy, we have reexamined the inhibitory properties of

  酰基-CoA 脱氢酶 (ACD) 是 FAD 依赖性酶，可催化适当的脂肪酰基-CoA 硫酯底物转化为相应的反式-α,β-烯酰基-CoA 产物。早期研究表明，脱氢是立体有择的，是通过提取 pro-R α-H 开始的，然后将 pro-R β-H 作为氢化物等价物转移到结合的 FAD 上。然而，最近关于次甘氨酸 A 的代谢物（亚甲基环丙基）乙酰辅酶 A（MCPA-CoA）使 ACD 失活的研究导致了另一种机制，其中还原当量从最初形成的 α-阴离子传递到结合FAD 通过单电子转移过程。为了进一步探索观察到的机制差异，我们重新检查了密切相关的 MCPA-CoA 类似物的抑制特性，螺戊基乙酰辅酶A（SPA-CoA），之前报道为ACD的紧密结合抑制剂。与早期结果相反，我们的数据显示 SPA-CoA 是一种基于机制的......
• Lai, Ming-Tain; Liu, Hung-Wen, Journal of the American Chemical Society, 1990, vol. 112, # 10, p. 4034 - 4035
  作者：Lai, Ming-Tain、Liu, Hung-Wen

  DOI：——

  日期：——
• 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.
• Stereospecific inactivation of the general acyl-CoA dehydrogenase from pig kidney by (R)-(-)-(methylenecyclopropyl)acetyl-CoA and (S)-(+)-(methylenecyclopropyl)acetyl-CoA
  作者：John E. Baldwin、Robert L. Ostrander、Clive D. Simon、Wayne C. Widdison

  DOI：10.1021/ja00161a069

  日期：1990.2
• Baldwin, John E.; Widdison, Wayne C., Journal of the American Chemical Society, 1992, vol. 114, # 6, p. 2245 - 2251
  作者：Baldwin, John E.、Widdison, Wayne C.

  DOI：——

  日期：——