cubylmethanol | 134078-23-2

• 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: cubylmethanol
• 英文别名: cubylcarbinol；cuban-1-ylmethanol
• CAS: 134078-23-2
• 化学式: C₉H₁₀O
• 分子量: 134.178
• InChiKey: SHBYTOJQOCOSPG-UHFFFAOYSA-N

物化性质

• 熔点：
  59-63 °C
• 沸点：
  260.2±8.0 °C(Predicted)
• 密度：
  1.691±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  cubylmethanol 在 三乙基硼氢化锂 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 methyl cubane
  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：

  4-甲氧羰基立方烷羧酸 在 sodium hydroxide 、 正丁基锂 、 碘苯二乙酸 、 dimethyl sulfide borane 、 碘 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 苯 为溶剂， 反应 9.41h， 生成 cubylmethanol
  参考文献：
  名称：

  Effective Synthetic Routes to Cubylcarbinol Derivatives

  摘要：

  介绍了从4-碘立方烷羧酸（5）合成立方基甲醇（1）的三条备选路线。

  DOI：

  10.1055/s-2002-35981

文献信息

• A Rapid and Mild Sulfation Strategy Reveals Conformational Preferences in Therapeutically Relevant Sulfated Xylooligosaccharides
  作者：Yen Vo、Brett D. Schwartz、Hideki Onagi、Jas S. Ward、Michael G. Gardiner、Martin G. Banwell、Keats Nelms、Lara R. Malins

  DOI：10.1002/chem.202100527

  日期：2021.7.7

  residues, as standards for biological studies. Near quantitative sulfation was accomplished using a remarkably mild and operationally simple protocol which avoids the need for high temperatures and a large excess of the sulfating reagent. Moreover, the sulfated xylooligomer standards so obtained enabled definitive identification of a pyridinium contaminant in a sample of a commercially prepared Pentosan

  虽然硫酸化木寡糖是有前途的治疗引线为病痛的多个，结构复杂性和非均质性的商业部署的形式（例如多硫酸戊聚糖1) 使他们进一步临床开发的道路复杂化。我们在本文中描述了迄今为止制备的最大的均质过硫酸化木寡聚体的合成，包括多达八个木糖残基，作为生物学研究的标准。使用非常温和且操作简单的方案完成了接近定量的硫酸化，该方案避免了对高温和大量过量硫酸化试剂的需要。此外，如此获得的硫酸化木寡聚体标准品能够明确鉴定商业制备的戊聚糖药物样品中的吡啶鎓污染物，并提供对成分过硫酸化单糖残基的构象偏好的重要见解。由于硫酸盐的空间分布是硫酸化寡糖与内源性靶标结合的关键决定因素，
• Cubanes in Medicinal Chemistry: Synthesis of Functionalized Building Blocks
  作者：Joanna Wlochal、Robert D. M. Davies、Jonathan Burton

  DOI：10.1021/ol501750k

  日期：2014.8.15

  cubane-1,4-dimethylester. A range of synthetic methods have been applied to prepare these cubane building blocks with one or two functional handles to allow easy incorporation into existing medicinal chemistry programs.

  从可商购的古巴-1,4-二甲基酯制备了一系列新的，药学上相关的含古巴分子。已经应用了多种合成方法来制备具有一个或两个功能手柄的这些古巴构建基块，以使其易于并入现有的药物化学程序中。
• 7-Azabicyclo[2.2.1]heptane as a scaffold for the development of selective sigma-2 (σ2) receptor ligands
  作者：Samuel D. Banister、Louis M. Rendina、Michael Kassiou

  DOI：10.1016/j.bmcl.2012.04.077

  日期：2012.6

  A series of N-substituted 7-azabicyclo[2.2.1]heptanes (12–17 and 22–25) and similarly substituted pyrrolidines (32–36 and 41–44) were synthesized as sterically-reduced, achiral analogs of adamantane- and trishomocubane-derived σ ligands. In vitro competition binding assays against σ receptors revealed that arylalkyl N-substituents conferred selectivity for the σ2 subtype, while alicyclic or polycarbocyclic

  合成了一系列的N-取代的7-氮杂双环[2.2.1]庚烷（12 – 17和22 – 25）和类似取代的吡咯烷（32 – 36和41 – 44），它们是经空间还原的金刚烷-和-的非手性类似物。从三栖古猿衍生的σ配体。体外竞争对σ受体结合测定法揭示的σ该芳基烷基的N-取代基赋予选择性2亚型，而脂环或多碳取代基赋予高亲和力对两种亚型。所述σ 2个的结合和选择性亚型Ñ-芳基烷基-7-氮杂降冰片烷通常比类似取代的吡咯烷大，这表明氮原子周围的空间体积和构象限制对亚型的识别很重要。
• 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
• Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere
  作者：Benjamin A. Chalmers、Hui Xing、Sevan Houston、Charlotte Clark、Sussan Ghassabian、Andy Kuo、Benjamin Cao、Andrea Reitsma、Cody‐Ellen P. Murray、Jeanette E. Stok、Glen M. Boyle、Carly J. Pierce、Stuart W. Littler、David A. Winkler、Paul V. Bernhardt、Cielo Pasay、James J. De Voss、James McCarthy、Peter G. Parsons、Gimme H. Walter、Maree T. Smith、Helen M. Cooper、Susan K. Nilsson、John Tsanaktsidis、G. Paul Savage、Craig M. Williams

  DOI：10.1002/anie.201510675

  日期：2016.3.7

  the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts

  制药和农用化学发现计划面临巨大的压力，以满足日益增长的全球需求，因此需要不断的创新。长期以来，经典的碳氢化合物支架一直在协助将新分子推向市场，但明显的遗漏是柏拉图式固体古巴。然而，伊顿认为该分子具有充当苯生物等排体的潜力。在本文中，我们报告了伊顿假说的验证，该假说是用五个分子的古巴衍生物在临床上或作为农药使用的。与它们的苯对应物相比，两种古巴类似物显示出更高的生物活性，而另外两种类似物显示出相同的生物活性，而第五种仅表现出部分功效。通过反思含有苯环的生物活性分子的数量，可以最好地实现这项研究的成果。在可能的情况下，用古巴棚架替代可以使这些系统恢复活力，从而加快了急需的潜在候选候选者的识别。