10β-(2-trimethylsilyloxyethyl)deoxoartemisinin | 540469-54-3

• 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: 10β-(2-trimethylsilyloxyethyl)deoxoartemisinin
• 英文别名: trimethyl-[2-[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]ethoxy]silane
• CAS: 540469-54-3
• 化学式: C₂₀H₃₆O₅Si
• 分子量: 384.588
• InChiKey: LZFOSQDZDGSURM-XYEKPRFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.48
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  间苯二甲醛 、 10β-(2-trimethylsilyloxyethyl)deoxoartemisinin 在 三氟甲磺酸三甲基硅酯 、 三乙基硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以58%的产率得到(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-[2-[[3-[2-[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]ethoxymethyl]phenyl]methoxy]ethyl]-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane
  参考文献：
  名称：

  Antimalarial and Antitumor Evaluation of Novel C-10 Non-Acetal Dimers of 10β-(2-Hydroxyethyl)deoxoartemisinin

  摘要：

  Four series of C-10 non-acetal dimers were prepared from key trioxane alcohol 10beta-(2-hydroxyethyl)deoxoartemisinin (9b). All of the dimers prepared displayed potent low nanomolar antimalarial activity versus the K1 and HB3 strains of Plasmodium falciparum. The most potent compound assayed was phosphate dimer 14a, which was greater than 50 times more potent than the parent drug artemisinin and about 15 times more potent than the clinically used acetal artemether. In contrast to their potent activity versus malaria parasites, virtually all of the dimers expressed poor anticancer activity apart from the trioxane phosphate ester dimers 14a and 14b, which expressed nanomolar growth inhibitory (GI(50)) values versus a range of cancer cell lines in the NCI 60 human cell line screen. Further detailed studies on these dimers in vitro in HL60 cells demonstrate that both phosphate ester dimers (14a and 14b) are more potent than the anticancer agent doxorubicin. Interestingly, phosphate ester monomers 9c and 9d, antimalarially active in the low nanomolar region versus P. falciparum, are inactive as anticancer agents even at concentrations in the millimolar region. This observation emphasizes the importance of two trioxane units for high antiproliferative activity, and we propose that the nature of the linker in dimers of this type plays a crucial role in imparting potent anticancer activity.

  DOI：

  10.1021/jm030974c
• 作为产物：
  描述：

  dihydroartemisinin 在 吡啶 、 4 A molecular sieve 、 臭氧 、 三乙胺 、 zinc(II) chloride 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 20.75h， 生成 10β-(2-trimethylsilyloxyethyl)deoxoartemisinin
  参考文献：
  名称：

  Antimalarial and Antitumor Evaluation of Novel C-10 Non-Acetal Dimers of 10β-(2-Hydroxyethyl)deoxoartemisinin

  摘要：

  Four series of C-10 non-acetal dimers were prepared from key trioxane alcohol 10beta-(2-hydroxyethyl)deoxoartemisinin (9b). All of the dimers prepared displayed potent low nanomolar antimalarial activity versus the K1 and HB3 strains of Plasmodium falciparum. The most potent compound assayed was phosphate dimer 14a, which was greater than 50 times more potent than the parent drug artemisinin and about 15 times more potent than the clinically used acetal artemether. In contrast to their potent activity versus malaria parasites, virtually all of the dimers expressed poor anticancer activity apart from the trioxane phosphate ester dimers 14a and 14b, which expressed nanomolar growth inhibitory (GI(50)) values versus a range of cancer cell lines in the NCI 60 human cell line screen. Further detailed studies on these dimers in vitro in HL60 cells demonstrate that both phosphate ester dimers (14a and 14b) are more potent than the anticancer agent doxorubicin. Interestingly, phosphate ester monomers 9c and 9d, antimalarially active in the low nanomolar region versus P. falciparum, are inactive as anticancer agents even at concentrations in the millimolar region. This observation emphasizes the importance of two trioxane units for high antiproliferative activity, and we propose that the nature of the linker in dimers of this type plays a crucial role in imparting potent anticancer activity.

  DOI：

  10.1021/jm030974c