10-azadeoxyartemisinin

• 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: 10-azadeoxyartemisinin
• 英文别名: (1S,4S,5R,8S,9R,12R,13R)-1,5,9-trimethyl-14,15-dioxa-11-azatetracyclo[10.2.1.04,13.08,13]pentadecan-10-one
• 化学式: C₁₅H₂₃NO₃
• 分子量: 265.353
• InChiKey: ADGGQIXWQTUBHU-NNWCWBAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  青蒿素 在 氨 、 硫酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 10-azadeoxyartemisinin
  参考文献：
  名称：

  Ring opening of artemisinin (qinghaosu) and dihydroartemisinin and interception of the open hydroperoxides with Formation of N-oxides — a chemical model for antimalarial mode of action

  摘要：

  In CH2Cl2 in the presence of benzylamine, artemisinin transfers an oxygen atom from the intermediate open hydroperoxide to tertiary amines to form N-oxides and N-benzyl-11-azadesoxyartemisinin Base-catalyzed side reactions interfere with the corresponding reaction involving dihydroartemisinin. The reactions serve as a model for biological activity in which the act of binding to a protein liberates hydroperoxide. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00830-8

文献信息

• New Products from the Reactions of Artemisinin with Ammonia and Amines
  作者：Ahmed M. Galal、M. Shamim Ahmad、Farouk S. El-Feraly、Andrew T. McPhail

  DOI：10.1021/np980142v

  日期：1999.1.1

  Reaction of artemisinin (1) with ammonia, methylamine, dimethylamine, and allylamine afforded five unexpected products 2-6, in addition to the previously reported compounds 7-12. The identities of the new compounds were established from their spectral data, by chemical derivatization and by comparison with published reports. The stereochemistries of compounds 5 and 6 were confirmed by single-crystal

  除了先前报道的化合物7-12以外，青蒿素（1）与氨，甲胺，二甲胺和烯丙基胺的反应还提供了5种出乎意料的产物2-6。通过光谱衍生数据，化学衍生化以及与已发表的报告进行比较，可以确定新化合物的身份。通过单晶X射线分析证实了化合物5和6的立体化学。
• 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.