(14S,S(S))-14-spiro-14α,21-sulfinyldioxytriptolide | 1060759-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧杂环己烷
• 英文名称: (14S,S(S))-14-spiro-14α,21-sulfinyldioxytriptolide
• 英文别名: (1'S,2S,2'S,4S,4'S,5'S,7'S,9'S,11'S,13'S)-1'-methyl-2-oxo-7'-propan-2-ylspiro[1,3,2-dioxathiolane-4,8'-3,6,10,16-tetraoxaheptacyclo[11.7.0.02,4.02,9.05,7.09,11.014,18]icos-14(18)-ene]-17'-one
• CAS: 1060759-86-5
• 化学式: C₂₁H₂₄O₈S
• 分子量: 436.483
• InChiKey: VWUBPXBMKDLNSR-MDQSAHDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  30
• 可旋转键数：
  1
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  119
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (14S,S(S))-14-spiro-14α,21-sulfinyldioxytriptolide 在 sodium periodate 、 ruthenium (III) chloride trihydrate 作用下， 以 水 、 乙腈 为溶剂， 反应 0.25h， 以86%的产率得到(14S)-14-spiro-14α, 21-sulfonyldioxytriptolide
  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
• 作为产物：
  描述：

  (14S)-14β-(hydroxymethyl)epitriptolide 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以43%的产率得到(14S,S(S))-14-spiro-14α,21-sulfinyldioxytriptolide
  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

文献信息

• Design and Synthesis of Novel C14-Hydroxyl Substituted Triptolide Derivatives as Potential Selective Antitumor Agents
  作者：Zheng Li、Zhao-Li Zhou、Ze-Hong Miao、Li-Ping Lin、Hui-Jin Feng、Lin-Jiang Tong、Jian Ding、Yuan-Chao Li

  DOI：10.1021/jm900342g

  日期：2009.8.27

  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.