(1R)-(-)-methylenecyclopropanecarboxylic acid | 30573-03-6

• 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)-(-)-methylenecyclopropanecarboxylic acid
• 英文别名: (1R)-methylenecyclopropanecarboxylic acid；(R)-(methylenecyclopropyl)formic acid；(R)-methylenecyclopropanecarboxylic acid；(1R)-2-methylidenecyclopropane-1-carboxylic acid
• CAS: 30573-03-6
• 化学式: C₅H₆O₂
• 分子量: 98.1014
• InChiKey: QJUQASYVMKRUMN-SCSAIBSYSA-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：

  (1R)-(-)-methylenecyclopropanecarboxylic acid 在 chromium(VI) oxide 、 sodium hydroxide 、 lithium aluminium deuteride 、 15-冠醚-5 、 硫酸 、 二异丁基氢化铝 、 三乙胺 作用下， 以 乙醚 、 正己烷 、 水 、 二甲基亚砜 、 丙酮 、 苯 为溶剂， 反应 6.0h， 生成 (+/-)-(2-methylenecyclopropyl)acetyl-α,α-d2-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：

  2-溴-2-甲基环丙烷-1-羧酸乙酯 在 氢氧化钾 、 乙醇 、 硫酸 、 sodium hydride 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 水 为溶剂， 反应 66.0h， 生成 (1R)-(-)-methylenecyclopropanecarboxylic acid
  参考文献：
  名称：

  （R）-（-）-和（S）-（+）-Synadenol：抗病毒作用的合成，绝对构型和对映选择性。

  摘要：

  描述了（R）-（-）-和（S）-（+）-香豆酚（1a和2a，95-6％ee）的合成。用腺苷脱氨酶将消旋的西地那醇（1a + 2a）脱氨基，得到（R）-（-）-synadenol（1a）和（S）-（+）-次黄嘌呤衍生物5。乙酰化后者化合物，得到乙酸酯6.与N，N-二甲基氯亚甲基氯化铵制得6-氯嘌呤衍生物7。氨解提供了（S）-（+）-synadenol（2a）。通过两种方法确定1a的绝对构型：（i）由（R）-亚甲基环丙烷羧酸（8）合成，以及（ii）（-）-香豆酚盐酸盐单晶的X射线衍射。外消旋的亚甲基环丙烷羧酸（10）通过描述的方法的改变而拆分。将R-对映异构体8转化为乙酯13，将其溴化，得到邻二溴化物14。用二异丁基氢化铝还原，然后得到醇15，将其乙酰化为相应的乙酸酯16。用16的腺嘌呤烷基化消除过程产生乙酸酯17和18。用氨脱保护得到R的Z-和E-异构体1a和19的混合物。 -配置。通过手性

  DOI：

  10.1021/jm980323u

文献信息

• 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
• 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。