8,19-Dihydroxy-5,7,9,11,16,18,20,22-octahydro-5,22:7,20:9,18:11,16-tetramethanononacene | 233588-13-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 8,19-Dihydroxy-5,7,9,11,16,18,20,22-octahydro-5,22:7,20:9,18:11,16-tetramethanononacene
• 英文别名: (1S,5R,9R,16S,20S,24R,28R,35S)-tridecacyclo[22.14.1.15,20.19,16.128,35.02,23.04,21.06,19.08,17.010,15.025,38.027,36.029,34]dotetraconta-2,4(21),6(19),7,10,12,14,17,22,25(38),26,29,31,33,36-pentadecaene-3,22-diol
• CAS: 233588-13-1
• 化学式: C₄₂H₃₀O₂
• 分子量: 566.699
• InChiKey: DSRJCCZUCSKSDS-FCODNRGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.02
• 重原子数：
  44.0
• 可旋转键数：
  0.0
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  40.46
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  8,19-Dihydroxy-5,7,9,11,16,18,20,22-octahydro-5,22:7,20:9,18:11,16-tetramethanononacene 在 ammonium hydroxide 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  [EN] NEW MOLECULAR TWEEZERS AGAINST NEUROLOGICAL DISORDERS AND VIRAL INFECTIONS
  [FR] NOUVELLES PINCES MOLÉCULAIRES CONTRE DES TROUBLES NEUROLOGIQUES ET DES INFECTIONS VIRALES

  摘要：

  在各种实施方式中，提供了新的分子钳化合物。本文所描述的化合物（例如分子钳）被认为有用于抑制蛋白质聚集（或使已聚集的蛋白质解聚）的作用。在某些实施方式中，本文所描述的化合物（例如分子钳）被认为有用于治疗由蛋白质聚集（例如淀粉样病变）所特征的病理状况，和/或用于治疗与急性创伤、中风等相关的脑或脊髓损伤，和/或用于治疗溶酶体贮积病，和/或用于治疗脂褐质相关疾病，以及各种病毒感染的作用。

  公开号：

  WO2020006489A1
• 作为产物：
  描述：

  8,19-Diacetoxy-5,7,9,11,16,18,20,22-octahydro-5,22:7,20:9,18:11,16-tetramethanononacene 在 lithium aluminium tetrahydride 作用下， 以98%的产率得到8,19-Dihydroxy-5,7,9,11,16,18,20,22-octahydro-5,22:7,20:9,18:11,16-tetramethanononacene
  参考文献：
  名称：

  赖氨酸和精氨酸的分子镊子

  摘要：

  赖氨酸和精氨酸在控制基因调控、糖蛋白靶向和囊泡转运等众多生物识别过程中起关键作用。它们还存在于负责例如细菌细胞壁生物合成、阿尔茨海默肽聚集和皮肤再生的信号肽序列中。迄今为止报道的所有人工受体结构中几乎没有一种对肽或蛋白质中的赖氨酸残基具有选择性和有效性。引入了一种人工分子镊子，它对赖氨酸具有极高的亲和力（K(a) 在中性磷酸盐缓冲液中约为 5000）。它的特点是一个富含电子的圆环形腔，装饰有两个外围的阴离子膦酸酯基团。精氨酸和赖氨酸的精确选择性是通过将整个氨基酸侧链穿过空腔并随后通过形成膦酸铵/胍盐桥锁定来实现的。这种类似假轮烷的几何结构也在小的碱性信号肽中形成，它们可以在缓冲水溶液中以前所未有的亲和力结合。NMR 滴定、NOESY 和 VT 实验以及 ITC 测量和 Monte Carlo 模拟一致指向一个焓驱动的过程，该过程利用范德华相互作用和构象锁的大量静电贡献的组合。由于 DMSO

  DOI：

  10.1021/ja052806a

文献信息

• Molecular Tweezers with Varying Anions: A Comparative Study
  作者：Som Dutt、Constanze Wilch、Thomas Gersthagen、Peter Talbiersky、Kenny Bravo-Rodriguez、Matti Hanni、Elsa Sánchez-García、Christian Ochsenfeld、Frank-Gerrit Klärner、Thomas Schrader

  DOI：10.1021/jo4009673

  日期：2013.7.5

  Selective binding of the phosphate-substituted molecular tweezer 1a to protein lysine residues was suggested to explain the inhibition of certain enzymes and the aberrant aggregation of amyloid petide A beta 42 or alpha-synuclein, which are assumed to be responsible for Alzheimer's and Parkinson's disease, respectively. In this work we systematically investigated the binding of four water-soluble tweezers 1a-d (substituted by phosphate, methanephosphonate, sulfate, or O-methylene-carboxylate groups) to amino acids and peptides containing lysine or arginine residues by using fluorescence spectroscopy, NMR spectroscopy, and isothermal titration calorimetry (ITC). The comparison of the experimental results with theoretical data obtained by a combination of QM/MM and ab initio H-1 NMR shift calculations provides clear evidence that the tweezers 1a-c bind the amino acid or peptide guest molecules by threading the lysine or arginine side chain through the tweezers cavity, whereas in the case of 1d the guest molecule is preferentially positioned outside the tweezer's cavity. Attractive ionic, CH-pi, and hydrophobic interactions are here the major binding forces. The combination of experiment and theory provides deep insight into the host-guest binding modes, a prerequisite to understanding the exciting influence of these tweezers on the aggregation of proteins and the activity of enzymes.
• Molecular Tweezers as Synthetic Receptors: Molecular Recognition of Electron-Deficient Aromatic and Aliphatic Substrates
  作者：Frank-Gerrit Klärner、Ulrich Burkert、Markus Kamieth、Roland Boese、Jordi Benet-Buchholz

  DOI：10.1002/(sici)1521-3765(19990604)5:6<1700::aid-chem1700>3.0.co;2-9

  日期：1999.6.4
• Molecular tweezers as synthetic receptors: molecular recognition of neutral and cationic aromatic substrates. A comparison between the supramolecular structures in crystal and in solution
  作者：Frank-Gerrit Kl�rner、Ulrich Burkert、Markus Kamieth、Roland Boese

  DOI：10.1002/1099-1395(200010)13:10<604::aid-poc271>3.0.co;2-7

  日期：2000.10

  The synthesis of substituted naphthalene- and benzene-spaced tweezer molecules Ib and c and 2e-j is reported. They selectively bind electron-deficient neutral and cationic aromatic substrates. The structural parameters of the substrate-receptor complexes derived from H-1 NMR measurements in solution are in good agreement with those obtained from single-crystal structure analyses. The tweezer 2f forms a stable complex with N,N-bis-(3,5-di-tert-butylbenzyl)-4,4'-bipyridinium 14, a substituted viologen dication, that exhibits the structure of a clipped rotaxane with a wheel opened on one side. The benzene-spaced tweezer 2j shows complexation of the cesium cation Cri inside the cavity. Copyright (C) 2000 John Wiley & Sons, Ltd.
• Molecular Clip and Tweezer Introduce New Mechanisms of Enzyme Inhibition
  作者：Peter Talbiersky、Frank Bastkowski、Frank-Gerrit Klärner、Thomas Schrader

  DOI：10.1021/ja801441j

  日期：2008.7.1

  Artificial molecular clips and tweezers, designed for cofactor and amino acid recognition, are able to inhibit the enzymatic activity of alcohol dehydrogenase (ADH). IC(50) values and kinetic investigations point to two different new mechanisms of interference with the NAD(+)-dependent oxidoreductase: While the clip seems to pull the cofactor out of its cleft, the tweezer docks onto lysine residues around the active site. Both modes of action can be reverted to some extent, by appropriate additives. However, while cofactor depletion by clip 1 was in part restored by subsequent NAD(+) addition, the tweezer (2) inhibition requires the competitive action of lysine derivatives. Lineweaver-Burk plots indicate a competitive mechanism for the clip, with respect to both substrate and cofactor, while the tweezer clearly follows a noncompetitive mechanism. Conformational analysis by CD spectroscopy demonstrates significant ADH denaturation in both cases. However, only the latter case (tweeze r-lysine) is reversible, in full agreement with the abovedetailed enzyme switch experiments. The complexes of ADH with clips or tweezer can be visualized in a nondenaturing gel electrophoresis, where the complexes migrate toward the anode, in contrast to the pure enzyme which approaches the cathode. Supramolecular chemistry has thus been employed as a means to control protein function-with the specificity of artificial hosts opening new avenues for this endeavor.