2-iodocubane-N,N-diisopropylcarboxamide | 94138-17-7

• 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: 2-iodocubane-N,N-diisopropylcarboxamide
• 英文别名: 2-iodo-N,N-di(propan-2-yl)cubane-1-carboxamide
• CAS: 94138-17-7
• 化学式: C₁₅H₂₀INO
• 分子量: 357.234
• InChiKey: AFMPYGLRTKTOFN-UHFFFAOYSA-N

物化性质

• 沸点：
  395.5±21.0 °C(predicted)
• 密度：
  1.69±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-iodocubane-N,N-diisopropylcarboxamide 在 ammonium hydroxide 、 potassium permanganate 、 lithium aluminium tetrahydride 、 草酰氯 、 (二氯碘)-苯 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.0h， 生成 2-chlorocubane-1-carboxamide
  参考文献：
  名称：

  生物活性分子发现中的古巴范式：进一步的范围，局限性和环辛酸酯的互补性。

  摘要：

  在广泛的研究中进一步探索了古巴苯环生物立体异构体范式，涵盖了广泛的药物和农用化学模板，其中包括抗生素（头孢克洛，青霉素G）和抗组胺药（苯海拉明），平滑肌松弛剂（金银花），麻醉剂（氯胺酮） ），农药杀虫剂（triflumuron），抗寄生虫药（苯并硝唑）和抗癌剂（他米巴罗汀）。这项研究从合成相容性和物理性质匹配两方面突出了将古巴人纳入生物活性分子发现的范围和局限性。在Chagas病抗寄生虫苯并硝唑的情况下，Cuban保持了生物等排作用，尽管在抗癌药（他米巴罗汀）方面活性较低。发现应用环辛酸酯（COT）（生物）基序补体相对于苯母体可优化苯硝唑，并在他米巴罗汀的情况下相对于古巴类似物具有增强的抗癌活性。像所有生物等排体，支架和生物基序一样，也存在局限性（例如合成实现），在此使用失败的示例对它们进行了特别强调。迄今为止，由我们小组准备的所有模板的摘要均经过了生物学评估，这强烈支持以下观点：古巴是生

  DOI：

  10.1039/c9ob01238a
• 作为产物：
  描述：

  N,N-diisopropylcubane-1-carboxamide 在 2,2,6,6-四甲基哌啶 、 正丁基锂 、 乙醚溴化镁 、 碘 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 18.0h， 生成 2-iodocubane-N,N-diisopropylcarboxamide
  参考文献：
  名称：

  生物活性分子发现中的古巴范式：进一步的范围，局限性和环辛酸酯的互补性。

  摘要：

  在广泛的研究中进一步探索了古巴苯环生物立体异构体范式，涵盖了广泛的药物和农用化学模板，其中包括抗生素（头孢克洛，青霉素G）和抗组胺药（苯海拉明），平滑肌松弛剂（金银花），麻醉剂（氯胺酮） ），农药杀虫剂（triflumuron），抗寄生虫药（苯并硝唑）和抗癌剂（他米巴罗汀）。这项研究从合成相容性和物理性质匹配两方面突出了将古巴人纳入生物活性分子发现的范围和局限性。在Chagas病抗寄生虫苯并硝唑的情况下，Cuban保持了生物等排作用，尽管在抗癌药（他米巴罗汀）方面活性较低。发现应用环辛酸酯（COT）（生物）基序补体相对于苯母体可优化苯硝唑，并在他米巴罗汀的情况下相对于古巴类似物具有增强的抗癌活性。像所有生物等排体，支架和生物基序一样，也存在局限性（例如合成实现），在此使用失败的示例对它们进行了特别强调。迄今为止，由我们小组准备的所有模板的摘要均经过了生物学评估，这强烈支持以下观点：古巴是生

  DOI：

  10.1039/c9ob01238a

文献信息

• A Protocol for an Iodine–Metal Exchange Reaction on Cubane Using Lithium Organozincates
  作者：Yumi Kato、Craig M. Williams、Masanobu Uchiyama、Seijiro Matsubara

  DOI：10.1021/acs.orglett.8b03721

  日期：2019.1.18

  The iodine–metal exchange reaction on cubane was examined using various lithium organozincates. Among these, the dianionic zincate, n-Bu4ZnLi2, gave optimum results. The resulting cubyl metal species could be converted into various cubane derivatives via addition reactions with electrophiles, such as an organohalide or aldehyde. The potential functional group tolerance of organozincates lends this

  使用各种有机锌锂检查了古巴对碘-金属的交换反应。其中，双阴离子锌酸盐n- Bu 4 ZnLi 2给出最佳结果。可以通过与亲电试剂（例如有机卤化物或醛）进行加成反应，将生成的立方金属物种转化为各种古巴衍生物。有机锌酸盐的潜在官能团耐受性使该方案适用于多官能化古巴衍生物的合成。
• Dimerization of Cubene. 1-Iodoadamantane as a Probe for Radical Intermediates
  作者：Kirill Lukin、Philip E. Eaton

  DOI：10.1021/ja00134a009

  日期：1995.7

  Fluoride ion induced elimination from 1-bromo- and 1-iodo-2-(trimethyisilyl)cubanes is shown to produce cubene (1) in excellent yield and at high enough concentration for its dimerization to propellane 16. This highly strained compound is unstable; the ultimate reaction pro ducts are characterized as the isomeric bis(tricyclo[4.2.0.0(2,5)]-octa-3,7-diene-3,8-diyl)s 11a,b. These are believed to form via a set of radical ring openings of 16. 1-Iodoadamantane is introduced as an iodine atom donor useful for probing the intermediacy of radicals in the chemistry of highly reactive, strained ring systems such as 16.
• 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.
• Systematic substitution on the cubane nucleus. Amide activation for metalation of "saturated" systems
  作者：Philip E. Eaton、Graziano Castaldi

  DOI：10.1021/ja00289a046

  日期：1985.2
• EATON, PH. E.;CASTALDI, G., J. AMER. CHEM. SOC., 1985, 107, N 3, 724-726
  作者：EATON, PH. E.、CASTALDI, G.

  DOI：——

  日期：——