(1S)-(-)-methylenecyclopropaneacetonitrile | 136060-98-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (1S)-(-)-methylenecyclopropaneacetonitrile
• 英文别名: 2-[(1S)-2-methylidenecyclopropyl]acetonitrile
• CAS: 136060-98-5
• 化学式: C₆H₇N
• 分子量: 93.1283
• InChiKey: WXYNOBHDRODNBH-ZCFIWIBFSA-N

物化性质

• 沸点：
  175.0±9.0 °C(Predicted)
• 密度：
  0.94±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.48
• 重原子数：
  7.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  23.79
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  (1S)-(-)-methylenecyclopropaneacetonitrile 在 chromium(VI) oxide 、 sodium hydroxide 、 硫酸 、 二异丁基氢化铝 、 三乙胺 作用下， 以 正己烷 、 水 、 丙酮 、 苯 为溶剂， 反应 4.84h， 生成 (S)-(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：

  亚甲基环丙烷-2-羧酸 在 lithium aluminium tetrahydride 、 15-冠醚-5 、 硫酸 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二甲基亚砜 为溶剂， 反应 9.17h， 生成 (1S)-(-)-methylenecyclopropaneacetonitrile
  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

文献信息

• Revision of Absolute Configuration of Enantiomeric (Methylenecyclopropyl)carbinols Obtained from (<i>R</i>)-(−)- and (<i>S</i>)-(+)-Epichlorohydrin and Methylenetriphenylphosphorane. Implications for Reaction Mechanism and Improved Synthesis of Antiviral Methylenecyclopropane Analogues of Nucleosides
  作者：Xinchao Chen、Jiri Zemlicka

  DOI：10.1021/jo010511j

  日期：2002.1.1

  reaction of (R)- and (S)-epichlorohydrin 5 with methylenetriphenylphosphorane or resolution of the corresponding oxaphospholane 6 via a salt with L-(+)-tartaric acid and subsequent Wittig transformation with formaldehyde were revised. The (-)-oxaphospholane 6 has the S,S and (-)-(methylenecyclopropyl)carbinol (4) the R configuration. The configurations of (+)-6 and (+)-4 are then R,R and S, respectively

  修订了通过（R）-和（S）-表氯醇5与亚甲基三苯基膦烷反应或通过与L-（+）-酒石酸的盐拆分相应的氧杂膦烷6并随后用甲醛进行Wittig转化而获得的对映异构体亚甲基环丙烷甲醇的绝对构型。（-）-氧杂膦烷6具有S，S和（-）-（亚甲基环丙基）甲醇（4）的R构型。那么（+）-6和（+）-4的构型分别是R，R和S。这些分配与环氧丙烷在环氧氯丙烷的环氧乙烷环上的初始攻击相符。还描述了改进的关键对映体中间体（R）-1a和（S）-1a的制备方法，对于合成核苷的抗病毒嘌呤亚甲基环丙烷类似物很重要。
• 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：——
• LAI, MING-TAIN;LIU, HUNG-WEN, J. AMER. CHEM. SOC., 112,(1990) N0, C. 4034-4035
  作者：LAI, MING-TAIN、LIU, HUNG-WEN

  DOI：——

  日期：——