ent-13-hydroxyl-15-kaurene-19-acid N-methylpiperazine ethyl ester

• 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: ent-13-hydroxyl-15-kaurene-19-acid N-methylpiperazine ethyl ester
• 英文别名: 2-(4-methylpiperazin-1-yl)ethyl (1R,4S,5R,9S,10S,13S)-13-hydroxy-5,9-dimethyl-14-methylidene-15-oxotetracyclo[11.2.1.01,10.04,9]hexadecane-5-carboxylate
• 化学式: C₂₇H₄₂N₂O₄
• 分子量: 458.641
• InChiKey: IDBVCALEWJCYPL-BMUFBPOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  甜叶菊甙元 在 叔丁基过氧化氢 、 selenium(IV) oxide 、 重铬酸吡啶 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.0h， 生成 ent-13-hydroxyl-15-kaurene-19-acid N-methylpiperazine ethyl ester
  参考文献：
  名称：

  ent-Kaurane Diterpenoids from Chinese Liverworts and Their Antitumor Activities through Michael Addition As Detected in Situ by a Fluorescence Probe

  摘要：

  It is generally accepted that the origin of the cytotoxicity of ent-kaurane diterpenoids is due to the formation of reactive oxygen species (ROS) and that the alpha,beta-unsaturated carbonyl is a pivotal moiety. Herein we demonstrate the isolation of 32 new and 12 known ent-kaurane diterpenoids from two Chinese liverworts. These compounds and three semisynthesized derivatives were screened against human cancer cell lines. The results revealed that their anticancer activities are caused by ROS formation through Michael modification of the protein thiols and depletion of glutathione unselectively. We also found that N-acetylcysteine reverses the cytotoxicity of these diterpenoids by forming Michael adducts, not through a well-recognized ROS scavenging pathway as previously reported. In situ intracellular thiol detection helped us visualize the intracellular distribution of the diterpenoids and determine the potency of their cytotoxicity. An alkaline analogue was found to be more selective because of the altered subcellular distribution.

  DOI：

  10.1021/acs.jmedchem.5b00208

文献信息

• <i>ent</i>-Kaurane Diterpenoids from Chinese Liverworts and Their Antitumor Activities through Michael Addition As Detected in Situ by a Fluorescence Probe
  作者：Zhaomin Lin、Yanxia Guo、Yanhui Gao、Shuqi Wang、Xiaoning Wang、Zhiyu Xie、Huanmin Niu、Wenqiang Chang、Lei Liu、Huiqing Yuan、Hongxiang Lou

  DOI：10.1021/acs.jmedchem.5b00208

  日期：2015.5.14

  It is generally accepted that the origin of the cytotoxicity of ent-kaurane diterpenoids is due to the formation of reactive oxygen species (ROS) and that the alpha,beta-unsaturated carbonyl is a pivotal moiety. Herein we demonstrate the isolation of 32 new and 12 known ent-kaurane diterpenoids from two Chinese liverworts. These compounds and three semisynthesized derivatives were screened against human cancer cell lines. The results revealed that their anticancer activities are caused by ROS formation through Michael modification of the protein thiols and depletion of glutathione unselectively. We also found that N-acetylcysteine reverses the cytotoxicity of these diterpenoids by forming Michael adducts, not through a well-recognized ROS scavenging pathway as previously reported. In situ intracellular thiol detection helped us visualize the intracellular distribution of the diterpenoids and determine the potency of their cytotoxicity. An alkaline analogue was found to be more selective because of the altered subcellular distribution.