(+/-)-myricanol | 68510-47-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (+/-)-myricanol
• 英文别名: myricanol；16,17-dimethoxytricyclo[12.3.1.12,6]nonadeca-1(17),2,4,6(19),14(18),15-hexaene-3,9,15-triol
• CAS: 68510-47-4
• 化学式: C₂₁H₂₆O₅
• 分子量: 358.434
• InChiKey: SBGBAZQAEOWGFT-UHFFFAOYSA-N

物化性质

• 沸点：
  583.5±50.0 °C(Predicted)
• 密度：
  1.208±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  79.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-myricanol 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以45%的产率得到(S)-8,9-dimethoxy-2,3,3a,4,5,6-hexahydro-1H-benzo[4,5]-cycloocta[1,2,3-de]naphthalene-7,11-diol
  参考文献：
  名称：

  Synthesis, Stereochemical Analysis, and Derivatization of Myricanol Provide New Probes That Promote Autophagic Tau Clearance

  摘要：

  We previously discovered that one specific scalemic preparation of myricanol (1), a constituent of Myrica cerifera (bayberry/southern wax myrtle) root bark, could lower the levels of the microtubule-associated protein tau (MAPT). The significance is that tau accumulates in a number of neurodegenerative diseases, the most common being Alzheimers disease (AD). Herein, a new synthetic route to prepare myricanol using a suitable boronic acid pinacol ester intermediate is reported. An X-ray crystal structure of the isolated myricanol (1) was obtained and showed a co-crystal consisting of (+)-aR,11S-myricanol (2) and (-)-aS,11R-myricanol (3) coformers. Surprisingly, 3, obtained from chiral separation from 1, reduced tau levels in both cultured cells and ex vivo brain slices from a mouse model of tauopathy at reasonable mid-to-low micromolar potency, whereas 2 did not. SILAC proteomics and cell assays revealed that 3 promoted tau degradation through an autophagic mechanism, which was in contrast to that of other tau-lowering compounds previously identified by our group. During the course of structureactivity relationship (SAR) development, we prepared compound 13 by acid-catalyzed dehydration of 1. 13 had undergone an unexpected structural rearrangement through the isomyricanol substitution pattern (e.g., 16), as verified by X-ray structural analysis. Compound 13 displayed robust tau-lowering activity, and, importantly, its enantiomers reduced tau levels similarly. Therefore, the semisynthetic analogue 13 provides a foundation for further development as a tau-lowering agent without its SAR being based on chirality.

  DOI：

  10.1021/cb501013w
• 作为产物：
  描述：

  杨梅酮 在 potassium tri-sec-butyl-borohydride 作用下， 以 四氢呋喃 为溶剂， 以80%的产率得到(+/-)-myricanol
  参考文献：
  名称：

  Synthesis, Stereochemical Analysis, and Derivatization of Myricanol Provide New Probes That Promote Autophagic Tau Clearance

  摘要：

  We previously discovered that one specific scalemic preparation of myricanol (1), a constituent of Myrica cerifera (bayberry/southern wax myrtle) root bark, could lower the levels of the microtubule-associated protein tau (MAPT). The significance is that tau accumulates in a number of neurodegenerative diseases, the most common being Alzheimers disease (AD). Herein, a new synthetic route to prepare myricanol using a suitable boronic acid pinacol ester intermediate is reported. An X-ray crystal structure of the isolated myricanol (1) was obtained and showed a co-crystal consisting of (+)-aR,11S-myricanol (2) and (-)-aS,11R-myricanol (3) coformers. Surprisingly, 3, obtained from chiral separation from 1, reduced tau levels in both cultured cells and ex vivo brain slices from a mouse model of tauopathy at reasonable mid-to-low micromolar potency, whereas 2 did not. SILAC proteomics and cell assays revealed that 3 promoted tau degradation through an autophagic mechanism, which was in contrast to that of other tau-lowering compounds previously identified by our group. During the course of structureactivity relationship (SAR) development, we prepared compound 13 by acid-catalyzed dehydration of 1. 13 had undergone an unexpected structural rearrangement through the isomyricanol substitution pattern (e.g., 16), as verified by X-ray structural analysis. Compound 13 displayed robust tau-lowering activity, and, importantly, its enantiomers reduced tau levels similarly. Therefore, the semisynthetic analogue 13 provides a foundation for further development as a tau-lowering agent without its SAR being based on chirality.

  DOI：

  10.1021/cb501013w

文献信息

• Convergent total synthesis of (±) myricanol, a cyclic natural diarylheptanoid
  作者：A. Bochicchio、L. Schiavo、L. Chiummiento、P. Lupattelli、M. Funicello、G. Hanquet、S. Choppin、F. Colobert

  DOI：10.1039/c8ob02052c

  日期：——

  myricanol in 9 steps and 4.9% overall yield starting from commercially available 2,3-dimethoxyphenol and methyl 3-(4-benzyloxyphenyl)propanoate. The key steps are a cross-metathesis to obtain a linear diarylheptanoid intermediate and a Suzuki–Miyaura domino reaction to generate the challenging macrocycle.

  据报道，杨梅醇的一种成分杨梅醇1可以降低微管相关蛋白tau（MAPT）的水平，该蛋白tau的积累在某些神经退行性疾病（例如阿尔茨海默氏病（AD））中起着重要作用。本文中，我们描述了一种新的合成路线，该路线可从9步制备丁香油，总收率为4.9％，从商业上可获得的2,3-二甲氧基苯酚和3-（4-苄氧基苯基）丙酸甲酯开始。关键步骤是交叉复分解以获得线性二芳基庚烷中间体和Suzuki-Miyaura多米诺反应以生成具有挑战性的大环。
• [EN] MEDICAMENT HAVING ANTI-INFLAMMATORY BOWEL DISEASE FUNCTION, AND PREPARATION METHOD THEREFOR AND APPLICATION THEREOF<br/>[FR] MÉDICAMENT PRÉSENTANT UNE FONCTION ANTI-MALADIE INTESTINALE INFLAMMATOIRE, SON PROCÉDÉ DE PRÉPARATION ET SON APPLICATION<br/>[ZH] 一种具有抗炎症性肠病作用的药物及其制备方法和应用
  申请人：SUZHOU PHARMAVAN CO LTD

  公开号：WO2020024078A1

  公开（公告）日：2020-02-06

  本申请提供了一种具有抗炎症性肠病作用的药物及其制备方法和应用，所述药物具有如式I或式II所示的结构，本申请所提供的药物及其药学上可接受的盐、溶剂合物、前药、互变异构体、立体化学异构体或药物组合物均对于炎症性肠病有良好的作用效果，可用于制备炎症性肠病的治疗药物，具有重要的临床意义和广泛的应用前景。
• Whiting, Donald A.; Wood, Andrew F., Journal of the Chemical Society. Perkin transactions I, 1980, p. 623 - 628
  作者：Whiting, Donald A.、Wood, Andrew F.

  DOI：——

  日期：——
• KRISHNAMURTY, H. G.;GHOSH, SANJUKTA;SATHYANARAYANA, S., INDIAN J. CHEM., 25,(1986) N 12, 1253-1254
  作者：KRISHNAMURTY, H. G.、GHOSH, SANJUKTA、SATHYANARAYANA, S.

  DOI：——

  日期：——
• Extensive 1D, 2D NMR Spectra of Some [7.0]Metacyclophanes and X-ray Analysis of (±)-Myricanol
  作者：Balawant S. Joshi、S. William Pelletier、M. Gary Newton、Doowon Lee、Georgia B. McGaughey、Mohindar S. Puar

  DOI：10.1021/np960230k

  日期：1996.1.1

  From the hexane extract of the bark of Myrica cerifera, the pentacyclic triterpenes taraxerol and myricadiol were isolated. The EtOH extract afforded the [7.0]metacyclophanes, (+/-)-myricanol(4), and myricanone (7). Accurate H-1- and C-13-NMR spectral assignments have been made for (+/-)-myricanol (4), 5,11,17-tri-O-acetyl-(+/-)-myricanol (5), 11-O-methyl-(+/-)-myricanol (6), and myricanone (7) by a study of the H-1-H-1-COSY, H-1-C-13-COSY (HETCOR), selective INEPT, and 1D NOE experiments. The structure of (+/-)-myricanol was established by a single crystal X-ray analysis. Molecular mechanics MM-3(94) calculations have been made for (R,Sa)- and (S,Sa)-myricanol, and the bond lengths, bond angles, and the torsion angles have been calculated for the energy-minimized conformation.