(S)-2-methylenecyclopropane-1-carboxylic acid | 30573-04-7

• 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: (S)-2-methylenecyclopropane-1-carboxylic acid
• 英文别名: (1S)-methylenecyclopropanecarboxylic acid；(S)-(methylenecyclopropyl)formic acid；(S)-methylenecyclopropanecarboxylic acid；(1S)-2-methylidenecyclopropane-1-carboxylic acid
• CAS: 30573-04-7
• 化学式: C₅H₆O₂
• 分子量: 98.1014
• InChiKey: QJUQASYVMKRUMN-BYPYZUCNSA-N

物化性质

• 沸点：
  197.1±9.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  7
• 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：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-2-methylenecyclopropane-1-carboxylic acid 在 lithium aluminium tetrahydride 、 15-冠醚-5 、 三乙胺 作用下， 以 乙醚 、 二甲基亚砜 为溶剂， 反应 1.17h， 生成 (1R)-(Methylenecyclopropyl)acetonitrile
  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 硫酸 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 生成 (S)-2-methylenecyclopropane-1-carboxylic acid
  参考文献：
  名称：

  (亚甲基环丙基)甲酰辅酶A灭活牛肝烯酰辅酶A水合酶的研究：灭活机制的阐明和半胱氨酸114作为包埋亲核试剂的鉴定

  摘要：

  （亚甲基环丙基）甲酰辅酶 A (MCPF-CoA) 是一种天然氨基酸（亚甲基环丙基）甘氨酸的代谢物，对牛肝烯酰辅酶 A 水合酶 (ECH) 的抑制特性进行了表征。我们之前已经证明 MCPF-CoA 专门针对 ECH，它催化 alpha,beta-不饱和烯酰-CoA 底物可逆地水合为相应的 β-羟酰基-CoA 产物。在这里，我们合成了 MCPF-CoA 的 (R)-和 (S)-非对映异构体，以检查这种失活的立体选择性。两种化合物均被证明是牛肝 ECH 的有效抑制剂，具有几乎相同的二级失活速率常数 (k(inact)/K(I)) 和分配比 (k(cat)/k(inact))，表明失活在环裂解方面是非立体特异性的。抑制剂，与牛肝 ECH 孵育后，在蛋白质活性位点附近标记胰蛋白酶肽 ALGGGXEL，其中 X 是共价修饰的氨基酸。牛肝 ECH 基因的克隆和序列分析揭示了被 MCPF-CoA 捕获的氨基酸残基的身份为

  DOI：

  10.1021/ja011226k

文献信息

• 2-hydroxymethylcyclopropylidenemethylpurines and -pyrimidines as antiviral agents
  申请人：Wayne State University

  公开号：US06352991B1

  公开（公告）日：2002-03-05

  Compounds which are active against viruses have the following Formulas: wherein B is a purine or pyrimidine heterocyclic ring and is preferably selected from the group consisting of 6-aminopurine (adenine), 2,6-diaminopurine, 2-amino-6-azidopurine, 2-amino-6-cyclopropylaminopurine, 6-hydroxypurine (hypoxanthine), 2-amino-6-halo substituted purines, 2-amino-6-alkoxy substituted purines, 2-amino-6-hydroxypurine (guanine), 3-deazapurines, 7-deaza-purines, 8-azapurines, cytosine, 5-halo substituted cytosines, 5-alkyl substituted cytosines, thymine, uracil and 6-azapyrimidines; X is O; and, R1 and R2 are alkyl or aryl groups. The compounds of the present invention also include the R- and S-enantiomers of the above compounds. The R1X and/or R2X can also be amino acid residues with X as NH.

  具有抗病毒活性的化合物具有以下配方：其中B是嘌呤或嘧啶杂环环，最好从包括6-氨基嘌呤（腺嘌呤）、2,6-二氨基嘌呤、2-氨基-6-偶氮基嘌呤、2-氨基-6-环丙胺基嘌呤、6-羟基嘌呤（次黄嘌呤）、2-氨基-6-卤代嘌呤、2-氨基-6-烷氧基嘌呤、2-氨基-6-羟基嘌呤（鸟嘌呤）、3-去氮嘌呤、7-去氮嘌呤、8-氮杂嘌呤、胞嘧啶、5-卤代胞嘧啶、5-烷基取代胞嘧啶、胸腺嘧啶、尿嘧啶和6-氮杂嘧啶中选择；X为O；R1和R2是烷基或芳基基团。本发明的化合物还包括上述化合物的R-和S-对映体。R1X和/或R2X也可以是带有X为NH的氨基酸残基。
• Synthesis of β-Cyclopropylalanines by Photolysis of Diacyl Peroxides
  作者：Rajendra P. Jain、John C. Vederas

  DOI：10.1021/ol035859a

  日期：2003.11.1

  [reaction: see text] Photolysis at 254 nm of neat (no solvent) unsymmetrical diacyl peroxides derived from cyclopropane carboxylic acids and l-aspartic acid generates protected beta-cyclopropylalanines in reasonable yields. Orthogonally protected 3-(trans-2-aminocyclopropyl)alanine (21), a key constituent of the antitumor agent belactosin A, as well as protected hypoglycin A (26), a causative agent

  [反应：参见正文] 254纳米（无溶剂）衍生自环丙烷羧酸和l-天冬氨酸的纯净（不溶剂）不对称二酰基过氧化物的光解以合理的收率生成了受保护的β-环丙基丙氨酸。通过这种方法，可以合成抗肿瘤药物贝洛糖素A的关键成分的正交保护的3-（反式-2-氨基环丙基）丙氨酸（21）和牙买加呕吐病的病原体受保护的次糖苷A（26）。中间取代的环丙基自由基的偶联主要在保留构型的情况下进行（dr>或= 95：5）。
• Studies on the Inactivation of Bovine Liver Enoyl-CoA Hydratase by (Methylenecyclopropyl)formyl-CoA:  Elucidation of the Inactivation Mechanism and Identification of Cysteine-114 as the Entrapped Nucleophile
  作者：Srikanth Dakoji、Ding Li、Gautam Agnihotri、Hui-qiang Zhou、Hung-wen Liu

  DOI：10.1021/ja011226k

  日期：2001.10.1

  (R)- and (S)-diastereomers of MCPF-CoA to examine the stereoselectivity of this inactivation. Both compounds were shown to be competent inhibitors for bovine liver ECH with nearly identical second-order inactivation rate constants (k(inact)/K(I)) and partition ratios (k(cat)/k(inact)), indicating that the inactivation is nonstereospecific with respect to ring cleavage. The inhibitor, upon incubation

  （亚甲基环丙基）甲酰辅酶 A (MCPF-CoA) 是一种天然氨基酸（亚甲基环丙基）甘氨酸的代谢物，对牛肝烯酰辅酶 A 水合酶 (ECH) 的抑制特性进行了表征。我们之前已经证明 MCPF-CoA 专门针对 ECH，它催化 alpha,beta-不饱和烯酰-CoA 底物可逆地水合为相应的 β-羟酰基-CoA 产物。在这里，我们合成了 MCPF-CoA 的 (R)-和 (S)-非对映异构体，以检查这种失活的立体选择性。两种化合物均被证明是牛肝 ECH 的有效抑制剂，具有几乎相同的二级失活速率常数 (k(inact)/K(I)) 和分配比 (k(cat)/k(inact))，表明失活在环裂解方面是非立体特异性的。抑制剂，与牛肝 ECH 孵育后，在蛋白质活性位点附近标记胰蛋白酶肽 ALGGGXEL，其中 X 是共价修饰的氨基酸。牛肝 ECH 基因的克隆和序列分析揭示了被 MCPF-CoA 捕获的氨基酸残基的身份为
• 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.