Myricanol | 181228-75-1

• 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: (+)-Ar,11S-Myricanol；(9S)-16,17-dimethoxytricyclo[12.3.1.12,6]nonadeca-1(17),2,4,6(19),14(18),15-hexaene-3,9,15-triol
• CAS: 181228-75-1
• 化学式: C₂₁H₂₆O₅
• 分子量: 358.434
• InChiKey: SBGBAZQAEOWGFT-HNNXBMFYSA-N

物化性质

• 熔点：
  205-206°C
• 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 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以75%的产率得到杨梅酮
  参考文献：
  名称：

  Bioactive Constituents of Chinese Natural Medicines. VII. Inhibitors of Degranulation in RBL-2H3 Cells and Absolute Stereostructures of Three New Diarylheptanoid Glycosides from the Bark of Myrica rubra.

  摘要：

  从中国杨梅树的树皮中分离出了三种新的日芳丙烯糖苷，分别命名为 (+)-S-美利卡醇 5-O-β-D-葡萄糖苷、桂皮醇 A 5-O-α-L-阿拉伯呋喃糖苷（1→6）-β-D-葡萄糖苷，以及桂皮醇 B 5-O-α-L-阿拉伯呋喃糖苷（1→6）-β-D-葡萄糖苷，同时还分离出了二十种已知化合物。新的日芳丙烯糖苷的绝对立体结构通过化学和物理化学证据明确，包括改进的莫舍尔法的应用。研究了分离化合物对 RBL-2H3 细胞中 β-氨基酮糖苷酶释放的抑制作用，发现几种日芳丙烯化合物、美利卡醇、(+)-S-美利卡醇、桂皮酮以及桂皮醇 A 和 B，还有一种黄酮类化合物美利克林，均表现出抑制活性。

  DOI：

  10.1248/cpb.50.208
• 作为产物：
  描述：

  (+)-S-myricanol 5-O-β-D-glucopyranoside 在 acetate buffer 、 β-glucosidase 作用下， 反应 48.0h， 以99%的产率得到Myricanol
  参考文献：
  名称：

  Bioactive Constituents of Chinese Natural Medicines. VII. Inhibitors of Degranulation in RBL-2H3 Cells and Absolute Stereostructures of Three New Diarylheptanoid Glycosides from the Bark of Myrica rubra.

  摘要：

  从中国杨梅树的树皮中分离出了三种新的日芳丙烯糖苷，分别命名为 (+)-S-美利卡醇 5-O-β-D-葡萄糖苷、桂皮醇 A 5-O-α-L-阿拉伯呋喃糖苷（1→6）-β-D-葡萄糖苷，以及桂皮醇 B 5-O-α-L-阿拉伯呋喃糖苷（1→6）-β-D-葡萄糖苷，同时还分离出了二十种已知化合物。新的日芳丙烯糖苷的绝对立体结构通过化学和物理化学证据明确，包括改进的莫舍尔法的应用。研究了分离化合物对 RBL-2H3 细胞中 β-氨基酮糖苷酶释放的抑制作用，发现几种日芳丙烯化合物、美利卡醇、(+)-S-美利卡醇、桂皮酮以及桂皮醇 A 和 B，还有一种黄酮类化合物美利克林，均表现出抑制活性。

  DOI：

  10.1248/cpb.50.208

文献信息

• [EN] MYRICANOL DERIVATIVES AND USES THEREOF FOR TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] DÉRIVÉS DE MYRICANOL ET LEURS UTILISATIONS POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：UNIV SOUTH FLORIDA

  公开号：WO2013152350A1

  公开（公告）日：2013-10-10

  The subject invention pertains to myricanol derivatives, therapeutic compositions, and methods for treatment of neurodegenerative diseases, in particular, neurodegenerative diseases associated with abnormal accumulation of protein tau.

  该发明涉及油松醇衍生物、治疗组合物和治疗神经退行性疾病的方法，特别是与蛋白质tau异常积累相关的神经退行性疾病。
• Myricanol Derivatives and Uses Thereof for Treatment of Neurodegenerative Diseases
  申请人：UNIVERSITY OF SOUTH FLORIDA

  公开号：US20150051294A1

  公开（公告）日：2015-02-19

  The subject invention pertains to myricanol derivatives, therapeutic compositions, and methods for treatment of neurodegenerative diseases, in particular, neurodegenerative diseases associated with abnormal accumulation of protein tau.

  本发明涉及myricanol衍生物、治疗组合物和治疗神经退行性疾病的方法，特别是与蛋白质tau异常积累相关的神经退行性疾病的治疗方法。
• Myricanol derivatives and uses thereof for treatment of neurodegenerative diseases
  申请人：University of South Florida

  公开号：US10287227B2

  公开（公告）日：2019-05-14

  The subject invention pertains to myricanol derivatives, therapeutic compositions, and methods for treatment of neurodegenerative diseases, in particular, neurodegenerative diseases associated with abnormal accumulation of protein tau.

  本发明涉及用于治疗神经退行性疾病，特别是与蛋白 tau 的异常积累有关的神经退行性疾病的 myricanol 衍生物、治疗组合物和方法。
• Synthesis, Stereochemical Analysis, and Derivatization of Myricanol Provide New Probes That Promote Autophagic Tau Clearance
  作者：Mackenzie D. Martin、Laurent Calcul、Courtney Smith、Umesh K. Jinwal、Sarah N. Fontaine、April Darling、Kent Seeley、Lukasz Wojtas、Malathi Narayan、Jason E. Gestwicki、Garry R. Smith、Allen B. Reitz、Bill J. Baker、Chad A. Dickey

  DOI：10.1021/cb501013w

  日期：2015.4.17

  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.
• MATERIALS AND METHODS FOR REDUCTION OF PROTEIN TAU AND TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：Dickey Chad

  公开号：US20130184353A1

  公开（公告）日：2013-07-18

  The subject invention provides a myricanol compound that is in predominant form of (+)-αR,11S-myricanol as compared to (−)-αS,11R-myricanol. In one embodiment, the (+)-αR,11S-myricanol is isolated from Myrica cerifera , and is in about 86% enantiomeric excess of (−)-αS,11R-myricanol. The subject invention also pertains to therapeutic compositions and methods for treatment of neurodegenerative diseases, in particular, neurodegenerative diseases associated with abnormal accumulation of protein tau. Specifically exemplified herein is the therapeutic use of myricanol and myricanone isolated from root barks of Myrica species. Also provided are methods for preparing extracts of the subject invention from Myrica species.