(5R,14S)-5α-hydroxy-14,21-epoxytriptolide | 1060759-66-1

• 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: (5R,14S)-5α-hydroxy-14,21-epoxytriptolide
• 英文别名: (14S)-5alpha-Hydroxytriptolide-14-spiro-1'-oxirane；(1S,2S,4S,5S,7S,8S,9S,11S,13R)-13-hydroxy-1-methyl-7-propan-2-ylspiro[3,6,10,16-tetraoxaheptacyclo[11.7.0.02,4.02,9.05,7.09,11.014,18]icos-14(18)-ene-8,2'-oxirane]-17-one
• CAS: 1060759-66-1
• 化学式: C₂₁H₂₄O₇
• 分子量: 388.417
• InChiKey: DZHQMLUIRXMDSJ-MHTMOWOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  28
• 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：
  96.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (14S)-14,21-epoxytriptolide 在 selenium(IV) oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以50%的产率得到(5R,14S)-5α-hydroxy-14,21-epoxytriptolide
  参考文献：
  名称：

  Semisynthesis of triptolide analogues: Effect of B-ring substituents on cytotoxic activities

  摘要：

  A series of B-ring modified analogues of triptolide were synthesized and tested for their cytotoxicity against two human tumor cell lines (U251 and PC-3). From the current investigation, the structure-cytotoxic activity relationships of these analogues suggested that the introduction of hydroxyl, epoxide, halogen or olefinic groups on C5 and/or C6 could still retain the cytotoxicity, albeit a little less potency, and the C7,C8-beta-epoxide group of triptolide was essential to its potent cytotoxic activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.069

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.
• Semisynthesis of triptolide analogues: Effect of B-ring substituents on cytotoxic activities
  作者：Hongtao Xu、Yi Chen、Huanyu Tang、Huijin Feng、Yuanchao Li

  DOI：10.1016/j.bmcl.2014.10.069

  日期：2014.12

  A series of B-ring modified analogues of triptolide were synthesized and tested for their cytotoxicity against two human tumor cell lines (U251 and PC-3). From the current investigation, the structure-cytotoxic activity relationships of these analogues suggested that the introduction of hydroxyl, epoxide, halogen or olefinic groups on C5 and/or C6 could still retain the cytotoxicity, albeit a little less potency, and the C7,C8-beta-epoxide group of triptolide was essential to its potent cytotoxic activity. (C) 2014 Elsevier Ltd. All rights reserved.