(12R,13R,14S)-12β-chloro-13α-hydroxy-14,21-epoxytriptolide | 1060759-83-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (12R,13R,14S)-12β-chloro-13α-hydroxy-14,21-epoxytriptolide
• 英文别名: (14S)-12-Deoxy-12beta-chloro-13alpha-hydroxytriptolide-14-spiro-1'-oxirane；(1S,2S,4R,5R,6R,7S,8S,10S,12S)-5-chloro-6-hydroxy-1-methyl-6-propan-2-ylspiro[3,9,15-trioxahexacyclo[10.7.0.02,4.02,8.08,10.013,17]nonadec-13(17)-ene-7,2'-oxirane]-16-one
• CAS: 1060759-83-2
• 化学式: C₂₁H₂₅ClO₆
• 分子量: 408.879
• InChiKey: HOYGMMCRBZAMJV-PDOWTACFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  28
• 可旋转键数：
  1
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  84.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (14S)-14,21-epoxytriptolide 在 盐酸 作用下， 以 水 、 丙酮 为溶剂， 反应 7.0h， 以39%的产率得到(12R,13R,14S)-12β-chloro-13α-hydroxy-14,21-epoxytriptolide
  参考文献：
  名称：

  Design and Synthesis of Novel C14-Hydroxyl Substituted Triptolide Derivatives as Potential Selective Antitumor Agents

  摘要：

  It has long been considered that the free beta hydroxyl group at C14 of triptolide(1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) ora five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14 beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum ill vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of I and also produces a promising anticancer drug candidate with unique anticancer activities.

  DOI：

  10.1021/jm900342g