15-(2,6-dimethoxyphenyl)-sclareol

• 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: 15-(2,6-dimethoxyphenyl)-sclareol
• 英文别名: (1R,2R,4aS,8aS)-1-[(E,3R)-5-(2,6-dimethoxyphenyl)-3-hydroxy-3-methylpent-4-enyl]-2,5,5,8a-tetramethyl-3,4,4a,6,7,8-hexahydro-1H-naphthalen-2-ol
• 化学式: C₂₈H₄₄O₄
• 分子量: 444.655
• InChiKey: XLTFUAATFNWSIZ-FWMJDOGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  58.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  香紫苏醇 、 2,6-二甲氧基苯硼酸 在 氧气 、 sodium acetate 、 palladium diacetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到15-(2,6-dimethoxyphenyl)-sclareol
  参考文献：
  名称：

  Design and Synthesis of Antitumor Heck-Coupled Sclareol Analogues: Modulation of BH3 Family Members by SS-12 in Autophagy and Apoptotic Cell Death

  摘要：

  Sclareol, a promising anticancer labdane diterpene, was isolated from Salvia sclarea. Keeping the basic stereochemistry-rich framework of the molecule intact, a method for the synthesis of novel sclareol analogues was designed using palladium(II)-catalyzed oxidative Heck coupling reaction in order to study their structureactivity relationship. Both sclareol and its derivatives showed an interesting cytotoxicity profile, with 15-(4-fluorophenyl)sclareol (SS-12) as the most potent analogue, having IC50 = 0.082 mu M against PC-3 cells. It was found that SS-12 commonly interacts with Bcl-2 and Beclin 1 BH3 domain proteins and enhances autophagic flux by modulating autophagy-related proteins. Moreover, inhibition of autophagy by autophagy inhibitors protected against SS-12-induced apoptosis. Finally, SS-12 effectively suppressed tumor growth in vivo in Ehrlichs ascitic and solid Sarcoma-180 mouse models.

  DOI：

  10.1021/jm501942m

文献信息

• Design and Synthesis of Antitumor Heck-Coupled Sclareol Analogues: Modulation of BH3 Family Members by SS-12 in Autophagy and Apoptotic Cell Death
  作者：Shakeel-u-Rehman、Bilal Rah、Shabir H. Lone、Reyaz Ur Rasool、Saleem Farooq、Debasis Nayak、Naveed Anjum Chikan、Souneek Chakraborty、Akanksha Behl、Dilip Manikaro Mondhe、Anindya Goswami、Khursheed Ahmad Bhat

  DOI：10.1021/jm501942m

  日期：2015.4.23

  Sclareol, a promising anticancer labdane diterpene, was isolated from Salvia sclarea. Keeping the basic stereochemistry-rich framework of the molecule intact, a method for the synthesis of novel sclareol analogues was designed using palladium(II)-catalyzed oxidative Heck coupling reaction in order to study their structureactivity relationship. Both sclareol and its derivatives showed an interesting cytotoxicity profile, with 15-(4-fluorophenyl)sclareol (SS-12) as the most potent analogue, having IC50 = 0.082 mu M against PC-3 cells. It was found that SS-12 commonly interacts with Bcl-2 and Beclin 1 BH3 domain proteins and enhances autophagic flux by modulating autophagy-related proteins. Moreover, inhibition of autophagy by autophagy inhibitors protected against SS-12-induced apoptosis. Finally, SS-12 effectively suppressed tumor growth in vivo in Ehrlichs ascitic and solid Sarcoma-180 mouse models.