11-<¹⁵N>azaartemisinin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 11-<¹⁵N>azaartemisinin
• 英文别名: (15N)-11-azaartemisinin；(1R,4S,5R,8S,9R,12R,13R)-1,5,9-trimethyl-14,15,16-trioxa-11-azatetracyclo[10.3.1.04,13.08,13]hexadecan-10-one
• 化学式: C₁₅H₂₃NO₄
• 分子量: 282.345
• InChiKey: LSHOKYZGSIIBMK-DEWSXILXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  青蒿素 在 ¹⁵N-ammonia 、 2,6-二叔丁基-4-甲基苯酚 、 硫酸 、 silica gel 作用下， 生成 10-<¹⁵N>azadesoxyartemisinin 、 11-<¹⁵N>azaartemisinin
  参考文献：
  名称：

  Syntheses and Antimalarial Activities of N-Substituted 11-Azaartemisinins

  摘要：

  A two-step reaction sequence between artemisinin and methanolic ammonia followed by treatment with Amberlyst 15 yielded 11-azaartemisinin in 65% yield. Substituting a variety of primary alkyl- and heteroaromatic amines for ammonia in the reaction sequence yields N-substituted 11-azaartemisinins in similar or greater yield. When Amberlyst 15 is replaced by a mixture of sulfuric acid/silica gel, both 11-azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin, are formed in 45% and 15% yields, respectively. In vitro and in vivo test data for a number of novel N-substituted 11-azaartemisinins, against drug-resistant strains of Plasmodium falciparum, show they possess antimalarial activities equal to or greater than that of artemisinin. The most active derivative, N-(2'-acetaldehydo)-11-azaartemisinin, 17, was 26 times more active in vitro and 4 times more active in vivo than artemisinin.

  DOI：

  10.1021/jm00026a012

文献信息

• Synthesis and reactions of 11-azaartemisinin and derivatives
  作者：Daniel S. Torok、Herman Ziffer

  DOI：10.1016/0040-4039(94)02419-c

  日期：1995.2

  11-Azaartemisinin was prepared in 454 yield in a one pot, two-step sequence from the reaction of artemisinin with excess ammonia followed by acid treatment Analogous reactions of artemisinin with primary alkylamines gave N-alkylazaartemisinins in similar yields.
• Syntheses and Antimalarial Activities of N-Substituted 11-Azaartemisinins
  作者：Daniel S. Torok、Herman Ziffer、Steven R. Meshnick、Xing-Qing Pan、Arba Ager

  DOI：10.1021/jm00026a012

  日期：1995.12

  A two-step reaction sequence between artemisinin and methanolic ammonia followed by treatment with Amberlyst 15 yielded 11-azaartemisinin in 65% yield. Substituting a variety of primary alkyl- and heteroaromatic amines for ammonia in the reaction sequence yields N-substituted 11-azaartemisinins in similar or greater yield. When Amberlyst 15 is replaced by a mixture of sulfuric acid/silica gel, both 11-azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin, are formed in 45% and 15% yields, respectively. In vitro and in vivo test data for a number of novel N-substituted 11-azaartemisinins, against drug-resistant strains of Plasmodium falciparum, show they possess antimalarial activities equal to or greater than that of artemisinin. The most active derivative, N-(2'-acetaldehydo)-11-azaartemisinin, 17, was 26 times more active in vitro and 4 times more active in vivo than artemisinin.