pentacyclo<5.4.0.0^2,6.0^3,10.0^5,9>-undecan-8,11-dione monoethyleneacetal | 58228-93-6

• 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: pentacyclo<5.4.0.0^2,6.0^3,10.0^5,9>-undecan-8,11-dione monoethyleneacetal
• 英文别名: pentacyclo<5.4.0.0^2,6.0^3,10.0^5,9>undecane-8,11-dione monoethylene ketal；pentacyclo<5.4.0.0^2,6.0^3,10.0^5,9>undecan-8,11-dione monoethylene ketal；spiro[1,3-dioxolane-2,8'-pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecan]-11'-one；pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane-8,11-dione ethylene acetal；octahydrospiro[2,4,1-(epiethane[1,1,2]triyl)cyclobuta[cd]pentalene-5,2'-[1,3]dioxolane]-7-one；pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane-8,11-dione monoethyleneacetal；Spiro[1,3-dioxolane-2,8'-pentacyclo[5.4.0.0^{2,6}.0^{3,10}.0^{5,9}]undecane]-11'-one；spiro[1,3-dioxolane-2,11'-pentacyclo[5.4.0.02,6.03,10.05,9]undecane]-8'-one
• CAS: 58228-93-6
• 化学式: C₁₃H₁₄O₃
• mdl: MFCD00180935
• 分子量: 218.252
• InChiKey: CBWMOBFPWMOJKZ-UHFFFAOYSA-N

物化性质

• 熔点：
  73.5-75.0 °C(Solv: ethyl ether (60-29-7))
• 沸点：
  371.7±42.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.923
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  pentacyclo<5.4.0.0^2,6.0^3,10.0^5,9>-undecan-8,11-dione monoethyleneacetal 在 chromium(VI) oxide 、 盐酸 、 sodium tetrahydroborate 、 溶剂黄146 、 potassium hydroxide 、 肼 作用下， 以 甲醇 、 乙醇 、 水 、 二乙二醇 为溶剂， 生成 五环[5.4.0.02,6.03,10.05,9]十一烷-8-酮
  参考文献：
  名称：

  Exploring the Requirements for the Hydrophobic Scaffold and Polar Amine in Inhibitors of M2 from Influenza A Virus

  摘要：

  Inhibitors targeting the influenza A virus M2 (A/M2) proton channel have lost their effectiveness due to widespread resistance. As a first step in the development of new inhibitors that address this problem, we have screened several focused collections of small molecules using two-electrode voltage patch clamp assays (TEVC) on Xenopus laevis oocytes. Diverse head groups and scaffolds of A/M2 inhibitors have been explored. It has been found that not only amine but also hydroxyl, aminooxyl, guanidine, and amidine compounds are active against the A/M2 proton channel. Moreover, the channel is able to accommodate a wide range of structural variation in the apolar scaffold. This study offers information to guide the next generation of A/M2 proton channel inhibitor design.

  DOI：

  10.1021/ml100297w
• 作为产物：
  描述：

  1,4,4 a,8 a-四氢-endo-1,4-甲烷萘-5,8-二酮 在 对甲苯磺酸 作用下， 以 苯 为溶剂， 反应 11.0h， 生成 pentacyclo<5.4.0.0^2,6.0^3,10.0^5,9>-undecan-8,11-dione monoethyleneacetal
  参考文献：
  名称：

  Design, synthesis and evaluation of pentacycloundecane and hexacycloundecane propargylamine derivatives as multifunctional neuroprotective agents

  摘要：

  The multifactorial pathophysiology of neurodegenerative disorders remains one of the main challenges in the design of a single molecule that may ultimately prevent the progression of these disorders in affected patients. In this article, we report on twelve novel polycyclic amine cage derivatives, synthesized with or without a propargylamine function, designed to possess inherent multifunctional neuroprotective activity. The mirr cytotoxicity assay results showed the SH-SY5Y human neuroblastoma cells to be viable with the twelve compounds, particularly at concentrations less than 10 mu M. The compounds also showed significant neuroprotective activity, ranging from 31% to 61% at 1 M, when assayed on SHSYSY human neuroblastoma cells in which neurodegeneration was induced by MPP+. Calcium regulation assays conducted on the same cell line showed the compounds to be significant VGCC blockers with activity ranging from 26.6% to 51.3% at 10 mu M; as well as significant NMDAr antagonists with compound 5 showing the best activity of 88.3% at 10 mu M. When assayed on human MAO isoenzymes, most of the compounds showed significant inhibitory activity, with compound 5 showing the best activity (MAO-B: IC50 = 1.70 mu M). Generally, the compounds were about 3-52 times more selective to the MAO-B isoenzyme than the MAO-A isoenzyme. Based on the time-dependency studies conducted, the compounds can be defined as reversible MAO inhibitors. Several structure activity relationships were derived from the various assays conducted, and the compounds' possible putative binding modes within the MAO-B enzyme cavity were assessed in silico. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.11.051

文献信息

• 1-methyl-(D3)-trishomocubane
  作者：T.G Dekker、D.W Oliver、Miss A Venter

  DOI：10.1016/s0040-4039(00)77419-3

  日期：1980.1

  The acid catalysed rearrangement of 8-methyl-pentacyclo(5.4.0.02,6.03,10.05,9)undecan-8-endo-o1 (8) to 3-methyl-(D3)-trishomocuban-4-o1 (9) provided the key step to the synthesis of the title compound (11).

  酸催化的8-甲基-五环（5.4.0.0 2,6 .0 3,10 .0 5,9）十一烷8-内切-o1（8）重排为3-甲基-（D 3）-三柔锰酸- 4-o1（9）提供了标题化合物（11）合成的关键步骤。
• Polycyclic amines as chloroquine resistance modulating agents in Plasmodium falciparum
  作者：Jacques Joubert、Erika Kapp、Dale Taylor、Peter J. Smith、Sarel F. Malan

  DOI：10.1016/j.bmcl.2016.01.052

  日期：2016.2

  either a PCU or adamantane amine moiety conjugated to different aromatic functionalities through various tethered linkers were selected based on their channel blocking abilities and evaluated as potential chemosensitizers. Compounds 2, 4, 5 and 10 showed significant voltage-gated calcium channel (VGCC) blocking ability (IC50 = 0.27–35 μM) and were able to alter the CQ IC50 in differing degrees (45–81%)

  五环十一烷基胺（PCU）和金刚烷胺，例如NGP1-01（1）和金刚烷胺，已显示出显着的通道阻断活性。假定它们起化学增敏剂的作用，并通过抑制p糖蛋白外排泵并使CQ在寄生虫消化液中积累，从而规避了疟原虫对氯喹（CQ）的抗性。根据十二烷基多环胺的通道阻断能力，选择十二种多环胺，这些多环胺含有通过各种束缚的接头与不同芳族官能团缀合的PCU或金刚烷胺部分，并被评估为潜在的化学增敏剂。化合物2，4，5和10显示出显着的电压门控钙通道（VGCC）阻断能力（IC 50  = 0.27–35μM），并且能够在具有多重耐药性的恶性疟原虫Dd2分离株中以不同程度（45–81％）改变CQ IC 50。其中，PCU-丹磺胺化合物（4）在1μM浓度（RMI = 0.19）时表现出对Dd2菌株起化学增敏作用的最佳潜力，同时显示出中等的抗血浆活性（Dd2 IC 50  = 6.25μM）和低对哺乳动物细胞系的体外细胞毒性（CHO，IC
• Synthesis of New Pentacyclo[5.4.0.02,6.03,10.05,9]undecane-8,11-dione (PCU) Cyanosilylated Derivatives Using Sulphated Zirconia and Hydrotalcite as Catalysts in Microwave-Assisted Reactions under Solvent Free Conditions
  作者：Nahí Adriana Guerra-Navarro、Laura Nadxieli Palacios-Grijalva、Deyanira Angeles-Beltrán、Guillermo E. Negrón-Silva、Leticia Lomas-Romero、Eduardo González-Zamora、Rubén Gaviño-Ramírez、Juan Navarrete-Bolaños

  DOI：10.3390/molecules16086561

  日期：——

  A comparison was made of the effectiveness of the functionalization reactions of pentacyclo[5.4.0.02,6.03,10.05,9]undecane-8,11-dione (PCU) using sulphated zirconia in protection-deprotection reactions and Mg/Al hydrotalcite in a cyanosilylation reaction, under classical thermal conditions and imposing microwave radiation; improved yields and reaction times were considered.

  比较了五环[5.4.0.02,6.03,10.05,9]十一烷-8,11-二酮（PCU）在保护-脱保护反应中使用硫酸化氧化锆和在氰基硅烷化中使用Mg/Al水滑石的官能化反应的有效性在经典热条件和施加微波辐射下的反应；考虑了改进的产率和反应时间。
• Synthesis and Binding Studies of Trishomocubanes: Novel Ligands for σ Binding Sites
  作者：Xiang Liu、Michael Kassiou、MacDonald J. Christie

  DOI：10.1071/ch99010

  日期：——

  Five new analogues of the σ2-selective trishomocubane N-(3′-fluorophenyl)methyl-4-azahexacyclo- [5.4.1.0 2;6 .0 3;10 .0 5;9 .0 8;11 ]dodecan-3-ol (2) have been synthesized and assessed for their anities at both σ1 and σ2 sites. The structural requirements which influence σ binding of functionalized trishomocubanes were investigated with a view to develop more potent σ ligands, with particular emphasis on the σ2 subtype. All synthesized compounds displayed moderate anity to σ binding sites. Binding at the σ1 site ranged from 107 to 1100 nМ while binding at the σ2 site ranged from 135 to 250 nМ. The subtype selectivity was influenced by the nature and position of substitution on the aromatic ring. Fluorine substitution in the meta position, as in (2), is favoured over ortho, or para or meta and para difluoro substitution for σ2 selectivity. Compounds (3)–(5) not only demonstrated lower anity at the σ2 site but a reversal of subtype selectivity with preferential binding at the σ1 site (σ1/σ2: 0 . 8 for (3); 0 . 4 for (4); 0 . 8 for (6)). Introduction of CF3 and NO2 groups into the meta position in compounds (6) and (7) retained σ2 selectivity although to a lesser extent when compared to (2) (σ1/σ2: 7 . 6 for (2); 2 . 0 for (6); 4 . 5 for (7)).

  五种新的 σ2-选择性三巯基甲苯的五个新类似物 N-(3′-氟苯基)甲基-4-氮杂己二环 [5.4.1.0 2;6 .0 3;10 .0 5;9 .0 8;11 ]十二烷-3-醇 (2) 的合成，并评估了它们在σ1 和σ2 中的活性。 σ1和 σ2位点的活性进行了评估。影响 的结构要求。 的结构要求进行了研究，以期开发出更有效的 有效的 σ 配体，特别强调了 σ2亚型。所有合成的 化合物都显示出对σ结合位点的适度敏感性。 结合位点。在 σ1 位点的结合力在 107 到 1100 nМ 之间，而在σ2 σ2位点的结合力为135至 250 nМ。亚型选择性受芳香环上取代的性质和位置的影响。 芳香环上的取代性质和位置对亚型选择性的影响。氟在 位上的氟取代（如 (2)）比 正位或对位或 对位和对位二氟 取代的σ2 选择性。化合物(3)-(5)不仅在σ2 位点的阳离子度较低，而且在σ2 位点的阳离子度较高。 σ2位点上的活性较低，而且亚型选择性发生了逆转 亚型选择性发生逆转，优先结合在 σ1位点 (σ1/σ2： 0 .8 对 (3)；0 .4 对 (4)；0 . 8 对 (6)）。将 在化合物 (6) 和 (7) 在化合物 (6) 和 (7) 的元位置上，保留了 σ2选择性，但与(2) 与 (2) 相比 (σ1/σ2： 7 .6 适用于 (2)； 2 .0 用于 (6)；4 .5 为 (7)).
• Synthesis and Biological Evaluations of NO-Donating Oxa- and Aza-Pentacycloundecane Derivatives as Potential Neuroprotective Candidates
  作者：Rajan Sharma、Jacques Joubert、Sarel Malan

  DOI：10.3390/molecules23020308

  日期：——

  In order to utilize the neuroprotective properties of polycyclic cage compounds, and explore the NO-donating ability of nitrophenyl groups, an array of compounds was synthesized where the different nitrophenyl groups were appended on oxa and aza-bridged cage derivatives. Biological evaluations of the compounds were done for cytotoxicity, neuroprotective abilities, the inhibition of N-methyl-d-aspartate (NMDA)-mediated Ca2+ influx, the inhibition of voltage-mediated Ca2+ influx, and S-nitrosylation abilities. All of the compounds showed low toxicity. With a few exceptions, most of the compounds displayed good neuroprotection and showed inhibitory activity for NMDA-mediated and voltage-gated calcium influx, ranging from high (>70%) to low (20–39%) inhibition. In the S-nitrosylation assay, the compounds with the nitro moiety as the NO-donating group exhibited low to good nitrosylation potency compared to the positive controls. From the biological evaluation of the tested compounds, it was not possible to obtain a simple correlation that could explain the results across all of the biological study domains. This can be ascribed to the independent processes evaluated in the different assays, which reiterate that neuroprotection is a result of multifactorial biochemical mechanisms and interactions. However, these results signify the important aspects of the pentacylcoundecylamine neuroprotectants across different biological study realms.

  为了利用多环笼状化合物的神经保护特性，并探究硝基苯基团的NO供体能力，合成了一系列化合物，其中不同的硝基苯基团被附加在氧和氮桥接的笼状衍生物上。对这些化合物进行了生物学评估，包括细胞毒性、神经保护能力、抑制N-甲基-D-天冬氨酸（NMDA）介导的Ca²⁺流入、抑制电压介导的Ca²⁺流入以及S-亚硝基化能力。所有化合物都显示出低毒性。除了少数例外，大多数化合物表现出良好的神经保护作用，并对NMDA介导和电压门控钙流入显示出抑制活性，抑制范围从高（>70%）到低（20-39%）。在S-亚硝基化试验中，带有硝基作为NO供体基团的化合物显示出与阳性对照相比从低到良好的亚硝基化效力。从对这些化合物的生物学评估中，无法获得一个简单的相关性来解释所有生物学研究领域的结果。这可以归因于在不同试验中评估的独立过程，这再次强调了神经保护是多因素生化机制和相互作用的结果。然而，这些结果表明了五环十一烷胺神经保护剂在不同生物学研究领域的重要方面。