N,N-diisopropylcubane-1-carboxamide | 94138-16-6

• 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: N,N-diisopropylcubane-1-carboxamide
• 英文别名: N,N-diisopropylcubanecarboxamide；N,N-di(propan-2-yl)cubane-1-carboxamide
• CAS: 94138-16-6
• 化学式: C₁₅H₂₁NO
• 分子量: 231.338
• InChiKey: MWLUVOILGCIBSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 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：

  N,N-diisopropylcubane-1-carboxamide 在 2,2,6,6-四甲基哌啶 、 lithium aluminium tetrahydride 、 正丁基锂 、 碘 、 二甲基二环氧乙烷 、 magnesium bromide 作用下， 以 四氢呋喃 、 乙醚 、 水 、 丙酮 、 正戊烷 为溶剂， 反应 22.58h， 生成 1-(2-甲基戊环[4.2.0.02,5.03,8.04,7]辛-1-基)乙酮
  参考文献：
  名称：

  Regiochemical Variations in Reactions of Methylcubane with tert-Butoxyl Radical, Cytochrome P-450 Enzymes, and a Methane Monooxygenase System

  摘要：

  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.

  DOI：

  10.1021/ja952226l
• 作为产物：
  描述：

  1-立方烷羧酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 21.0h， 生成 N,N-diisopropylcubane-1-carboxamide
  参考文献：
  名称：

  通过古巴的价异构化环辛酸酯：范围和局限性

  摘要：

  在官能团耐受性，多重取代模式和古巴酒精经历一锅串联Ley-Griffith的能力的背景下，研究了伊顿铑（I）催化的古巴价氢异构化为环辛三烯（COT）的范围和局限性在没有过渡金属催化剂的情况下进行维蒂希反应。

  DOI：

  10.1002/chem.201805124

文献信息

• The cubane paradigm in bioactive molecule discovery: further scope, limitations and the cyclooctatetraene complement
  作者：Sevan D. Houston、Tyler Fahrenhorst-Jones、Hui Xing、Benjamin A. Chalmers、Melissa L. Sykes、Jeanette E. Stok、Clementina Farfan Soto、Jed M. Burns、Paul V. Bernhardt、James J. De Voss、Glen M. Boyle、Maree T. Smith、John Tsanaktsidis、G. Paul Savage、Vicky M. Avery、Craig M. Williams

  DOI：10.1039/c9ob01238a

  日期：——

  antibiotics (cefaclor, penicillin G) and antihistamine (diphenhydramine), a smooth muscle relaxant (alverine), an anaesthetic (ketamine), an agrochemical instecticide (triflumuron), an antiparasitic (benznidazole) and an anticancer agent (tamibarotene). This investigation highlights the scope and limitations of incorporating cubane into bioactive molecule discovery, both in terms of synthetic compatibility

  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
• 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。
• Cubane Chirality via Substitution of a “Hidden” Regular Tetrahedron
  作者：Nana Yoshino、Yumi Kato、Thibaud Mabit、Yuuya Nagata、Craig M. Williams、Mei Harada、Atsuya Muranaka、Masanobu Uchiyama、Seijiro Matsubara

  DOI：10.1021/acs.orglett.0c01142

  日期：2020.6.5

  class of chiral molecules. In pursuit of this endeavor, we prepared 1,3-dibromo-4-deuteriocubane-N,N-diisopropylcarboxamide, which upon treatment with zincates affords 1,3,5-trisubstituted cubanes via simultaneous two-position substitution reactions. The proposed chiral attributes of this stereogeometric class were confirmed by enantiomeric resolution of a p-bromobenzyl derivative using chiral HPLC.

  在六面体烃古巴仑中，在内部四面体中任何一个内的三个位置上的氢原子替换为其他原子，从概念上讲可以导致形成一类独特的手性分子。为了实现这一目标，我们制备了1,3-二溴-4-氘代库氏菌-N，N-二异丙基羧酰胺，用锌酸盐处理后，可通过同时进行的两个位置取代反应提供1,3,5-三取代的库氏菌。此stereogeometric类的所提出的手性属性被通过的对映体拆分证实p -bromobenzyl衍生物利用手性HPLC。
• Unmasking Inherent Chirality within the Cubane Skeleton
  作者：Nana Yoshino、Yumi Kato、Yukako Shimada、Craig M. Williams、Seijiro Matsubara

  DOI：10.1002/ijch.202100013

  日期：2021.7

  Cubane, a hexahedral hydrocarbon, can be converted into an asymmetric molecule with a minimum of three substituents. The resulting chiral cubane can be used as a pharmacophore or a chiral ligand. Starting from the cubane carboxamide, the 1,2,3-substituted compound was synthesized by sequential ortho-metalation. The 1,3,5-substituted compound was synthesized by combining site-selective halogenation

  古巴烷是一种六面体烃，可以转化为具有最少三个取代基的不对称分子。所得手性立方烷可用作药效团或手性配体。从立方甲酰胺开始，1,2,3-取代的化合物通过顺序邻位金属化合成。1,3,5-取代的化合物通过结合位点选择性卤化和卤素-金属交换合成，所得外消旋物通过HPLC进行对映体拆分。
• Chiral Auxiliary-Directed Site-Selective Deprotonation of the Cubane Skeleton
  作者：Hiyori Takebe、Nana Yoshino、Yukako Shimada、Craig M. Williams、Seijiro Matsubara

  DOI：10.1021/acs.orglett.2c03659

  日期：2023.1.13

  The first diastereoselective synthesis of trisubstituted cubanes was achieved using a chiral auxiliary. To establish chirality within the cubane skeleton, at least three substituents must be introduced at the appropriate positions. Ready conversion of cubane carboxylic acid to a chiral amide followed by sequential ortho-selective deprotonations and electrophilic trapping afforded the corresponding

  三取代立方烷的首次非对映选择性合成是使用手性助剂实现的。为了在立方烷骨架内建立手性，必须在适当的位置引入至少三个取代基。将立方烷羧酸快速转化为手性酰胺，然后依次进行邻位选择性去质子化和亲电捕获，得到相应的具有高非对映选择性的 1,2,3-三取代立方烷。这条路线为制备富含对映体的立方烷开辟了新的可能性。