Chinese Journal of Organic Chemistry ›› 2019, Vol. 39 ›› Issue (10): 2860-2866.DOI: 10.6023/cjoc201902024 Previous Articles     Next Articles

ARTICLES

N-水杨醛腙修饰11-氮杂青蒿素衍生物的合成及性质研究

李四聪a, 季绍聪b, 赵亮a, 廖晓雨b, 刘传峰a, 汤浩东a, 舒正宁a, 杨鹏a*(), 裴月湖b*()   

  1. a 沈阳药科大学无涯学院 沈阳 110016
    b 沈阳药科大学中药学院 沈阳 110016
  • 收稿日期:2019-02-22 修回日期:2019-04-29 出版日期:2019-10-25 发布日期:2019-06-06
  • 通讯作者: 杨鹏,裴月湖 E-mail:yangpeng@syphu.edu.cn;peiyueh@vip.163.com
  • 基金资助:
    辽宁省自然科学基金(20180550874)

Syntheses and Property Evaluation of N-Salicylaldehyde Hydrazone Modified 11-Azaartemisinins and Their Derivatives

Li, Siconga, Ji, Shaocongb, Zhao, Lianga, Liao, Xiaoyub, Liu, Chuanfenga, Tang, Haodonga, Shu, Zhengninga, Yang, Penga*(), Pei, Yuehub*()   

  1. a Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016
    b School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016
  • Received:2019-02-22 Revised:2019-04-29 Online:2019-10-25 Published:2019-06-06
  • Contact: Yang, Peng,Pei, Yuehu E-mail:yangpeng@syphu.edu.cn;peiyueh@vip.163.com
  • Supported by:
    Project supported by the Natural Science Foundation of Liaoning Province(20180550874)

N-Salicylaldehyde hydrazone modified 11-azaartemisinins and their deoxy analogues were designed and synthesized. By using various techniques including UV-vis, fluorescence, NMR as well as molecular modeling, the conformations of (3R,5aS,6R,8aS,9R,12S,12aR)-11-(((E)-2-hydroxy-5-(4-hydroxy-3-((E)-(((3R,5aS,6R,8aS,9R,12R,12aR)-3,6,9-trimethyl-10- oxodecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isoquinolin-11(12H)-yl)imino)methyl)benzyl)benzylidene)amino)-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isoquinolin-10(3H)-one (3) was analyzed, the binding behavior between 3 and hemin was measured, and the solubility-enhancing property of 3 by calix[4]carbazole was evaluated. The results show that the intramolecular hydrogen binding between the N atom of Schiff base in N-salicylaldehyde hydrazone bond and the OH favors the formation of tweezer-like conformation of 3, which enables it to interact with hemin in 1∶1 ratio. Moreover, the poor solubility of 3 in water could be enhanced due to its interaction with calix[4]carbazole, which pave the way for the further evaluation of the bioactivities of 3 in the future.

Key words: macrocycle, molecular recognition, carbazole, artemisinin