[(2S,11S,11aR)-10-(acetyloxymethyl)-2-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-5-oxo-1,2,3,6,11,11a-hexahydropyrrolo[2,1-b][3]benzazepin-11-yl] benzoate | 1255794-70-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(2S,11S,11aR)-10-(acetyloxymethyl)-2-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-5-oxo-1,2,3,6,11,11a-hexahydropyrrolo[2,1-b][3]benzazepin-11-yl] benzoate
• CAS: 1255794-70-7
• 化学式: C₃₉H₃₆N₂O₉
• 分子量: 676.723
• InChiKey: KBCXBMZOOIOBGY-OKKLIPQLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  50
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  149
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 10.0h， 以7 mg的产率得到[(2S,11S,11aR)-10-(acetyloxymethyl)-2-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-5-oxo-1,2,3,6,11,11a-hexahydropyrrolo[2,1-b][3]benzazepin-11-yl] benzoate
  参考文献：
  名称：

  Design and synthesis of de novo cytotoxic alkaloids by mimicking the bioactive conformation of paclitaxel

  摘要：

  Novel paclitaxel-mimicking alkaloids were designed and synthesized based on a bioactive conformation of paclitaxel, that is, REDOR-Taxol. The alkaloid 2 bearing a 5-7-6 tricyclic scaffold mimics REDOR-Taxol best among the compounds designed and was found to be the most potent compound against several drug-sensitive and drug-resistant human cancer cell lines. MD simulation study on the paclitaxel mimics 1 and 2 as well as REDOR-Taxol bound to the 1JFF tubulin structure was quite informative to evaluate the level of mimicking. The MD simulation study clearly distinguishes the 5-6-6 and 5-7-6 tricyclic scaffolds, and also shows substantial difference in the conformational stability of the tubulin-bound structures between 2 and REDOR-Taxol. The latter may account for the large difference in potency, and provides critical information for possible improvement in the future design of paclitaxel mimics. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.069

文献信息

• Design and synthesis of de novo cytotoxic alkaloids by mimicking the bioactive conformation of paclitaxel
  作者：Liang Sun、Jean M. Veith、Paula Pera、Ralph J. Bernacki、Iwao Ojima

  DOI：10.1016/j.bmc.2010.07.069

  日期：2010.10

  Novel paclitaxel-mimicking alkaloids were designed and synthesized based on a bioactive conformation of paclitaxel, that is, REDOR-Taxol. The alkaloid 2 bearing a 5-7-6 tricyclic scaffold mimics REDOR-Taxol best among the compounds designed and was found to be the most potent compound against several drug-sensitive and drug-resistant human cancer cell lines. MD simulation study on the paclitaxel mimics 1 and 2 as well as REDOR-Taxol bound to the 1JFF tubulin structure was quite informative to evaluate the level of mimicking. The MD simulation study clearly distinguishes the 5-6-6 and 5-7-6 tricyclic scaffolds, and also shows substantial difference in the conformational stability of the tubulin-bound structures between 2 and REDOR-Taxol. The latter may account for the large difference in potency, and provides critical information for possible improvement in the future design of paclitaxel mimics. (C) 2010 Elsevier Ltd. All rights reserved.