4-Methylcubancarbonsaeurechlorid | 60462-16-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 4-Methylcubancarbonsaeurechlorid
• 英文别名: 4-Methylcubane-1-carbonyl chloride
• CAS: 60462-16-0
• 化学式: C₁₀H₉ClO
• 分子量: 180.634
• InChiKey: FRIBSHXDKVJXRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-Methylcubancarbonsaeurechlorid 在 cytochrome P₄₅₀ CYP₁₀₁B₁ from Novosphingobium aromaticivorans DSM 12444 、 还原型辅酶Ⅰ 、 bovine liver catalase 作用下， 以 乙醚 为溶剂， 反应 10.5h， 生成 4-hydroxymethylcubane-1-acetic acid methyl ester
  参考文献：
  名称：

  细胞色素 P450 对甲基立方烷进行无重排羟基化：C-H 提取和反弹动态耦合的案例

  摘要：

  通过切断立方体的两个键，高度应变的立方甲基自由基经历了已知最快的自由基重排之一（据报道，在 25°C 下 k = 2.9 × 1010 s-1）。这种重排以前已被用作机械探针来检测酶催化 CH 氧化中基于自由基的途径。本文报道了高选择性细胞色素 P450 催化的甲基立方氧化的发现，其理论上通过立方甲基自由基中间体进行，但显着没有重排。发现来自新鞘氨醇 DSM 12444 的细菌细胞色素 P450 CYP101B1 可将一系列含有区域导向羰基官能团的甲基立方底物的甲基羟基化到 C-4。与其他报道的 P450 催化的甲基立方氧化不同，设计的甲基古巴烷以高效和选择性羟基化，产生高达 93% 的立方甲醇。立方环开环的缺乏意味着在这些 CYP101B1 催化的羟基化过程中形成的立方甲基自由基必须具有非常短的寿命，只有几皮秒，这对于它们来说太短，无法表现出完全平衡的 P450 中间体的副反应特征。我们

  DOI：

  10.1021/jacs.9b08064
• 作为产物：
  描述：

  1,4-二碘五环[4.2.0.02,5.03,8.04,7]辛烷 在 氯化亚砜 、 叔丁基锂 作用下， 以 四氢呋喃 、 乙醚 、 正戊烷 为溶剂， 反应 18.58h， 生成 4-Methylcubancarbonsaeurechlorid
  参考文献：
  名称：

  细胞色素 P450 对甲基立方烷进行无重排羟基化：C-H 提取和反弹动态耦合的案例

  摘要：

  通过切断立方体的两个键，高度应变的立方甲基自由基经历了已知最快的自由基重排之一（据报道，在 25°C 下 k = 2.9 × 1010 s-1）。这种重排以前已被用作机械探针来检测酶催化 CH 氧化中基于自由基的途径。本文报道了高选择性细胞色素 P450 催化的甲基立方氧化的发现，其理论上通过立方甲基自由基中间体进行，但显着没有重排。发现来自新鞘氨醇 DSM 12444 的细菌细胞色素 P450 CYP101B1 可将一系列含有区域导向羰基官能团的甲基立方底物的甲基羟基化到 C-4。与其他报道的 P450 催化的甲基立方氧化不同，设计的甲基古巴烷以高效和选择性羟基化，产生高达 93% 的立方甲醇。立方环开环的缺乏意味着在这些 CYP101B1 催化的羟基化过程中形成的立方甲基自由基必须具有非常短的寿命，只有几皮秒，这对于它们来说太短，无法表现出完全平衡的 P450 中间体的副反应特征。我们

  DOI：

  10.1021/jacs.9b08064

文献信息

• Proton magnetic resonance spectra of cubane derivatives. I. Syntheses and spectra of mono- and 1,4-disubstituted cubanes
  作者：John T. Edward、Patrick G. Farrell、Gordon E. Langford

  DOI：10.1021/ja00427a003

  日期：1976.5
• Regiochemical Variations in Reactions of Methylcubane with <i>tert</i>-Butoxyl Radical, Cytochrome P-450 Enzymes, and a Methane Monooxygenase System
  作者：Seung-Yong Choi、Philip E. Eaton、Paul F. Hollenberg、Katherine E. Liu、Stephen J. Lippard、Martin Newcomb、David A. Putt、Subhash P. Upadhyaya、Yusheng Xiong

  DOI：10.1021/ja952226l

  日期：1996.1.1

  Reactions of methylcubane (1) with the tert-butoxyl radical (t-BuO.), with cytochrome P-450 enzymes, and with a methane monooxygenase (MMO) system have been studied. For the purpose of product characterization, authentic samples of 2-methylcubyl and 4-methylcubyl derivatives were prepared. 2-Methylcubanecarboxylic acid (9b) is a new compound prepared from cubanecarboxylic acid. The key synthetic reactions were (1) metalation and subsequent iodination of the 2-position of (diisopropylcarbamoyl)cubane to effect the initial functionalization, (2) lithium-for-iodine exchange and methylation followed by reduction to give 2-methyl-1-[(diisopropylamino)methyl]-cubane, and (3) dimethyldioxirane oxidation of this amine to give 9b. The known 4-methylcubanecarboxylic acid (9d) was prepared here by a route related to that employed for 9b. Reactions of acids 9b and 9d with methyllithium gave the corresponding methyl ketones which were oxidized by m-chloroperoxybenzoic acid to provide authentic samples of 2- and 4-methylcubanol acetates (3b and 3d). Reaction of 1 with t-BuO(.) in the presence of 2,2,5,5-tetramethylisoindole-N-oxyl radical (TMIO(.)) at 40-55 degrees C gave mainly cube-substituted products in confirmation of the report (Della, E. W.; Head, N. J.; Mallon, P.; Walton, J. C. J. Am. Chem. Sec. 1992, 114, 10730) that hydrogen atom abstraction by the electrophilic alkoxyl radical at low temperature occurs at the cubyl C-H positions. In a competition experiment at 42 degrees C, methylcubane was at least 3.5 times more reactive toward t-BuO(.) than cyclohexane, indicating that the cubyl positions in 1 are greater than or equal to 40 times more reactive than the methyl positions in 1 (per hydrogen) toward the alkoxyl radical. Oxidation of 1 by enzymes gave alcohol products that were converted to their acetate derivatives for identification and quantitation. Microsomal cytochrome P-450 enzymes from rat and the rat purified P-450 isozyme CYP2B1 hydroxylated 1 at all positions, whereas the reconstituted MMO system from Methylococcus capsulatus (Bath) hydroxylated 1 only at the methyl position. The differences in regioselectivity suggest that the transition states for hydrogen abstraction by the alkoxyl radical and for enzyme-catalyzed hydroxylation differ considerably. The results are consistent with a model for concerted enzyme catalyzed hydroxylation of 1 involving ''side-on'' approach to the C-H bond of substrate.