有机化学 ›› 2021, Vol. 41 ›› Issue (2): 708-718.DOI: 10.6023/cjoc202008006 上一篇    下一篇

研究论文

含喹唑啉硫醚的杨梅素衍生物的设计、合成及生物活性研究

贺军1, 唐雪梅1, 周清1, 彭峰1, 刘婷婷1, 柳立伟1, 贺鸣1, 谢承卫1, 薛伟1,*()   

  1. 1 贵州大学精细化工研究开发中心 绿色农药与农业生物工程国家重点实验室培育基地 教育部绿色农药与生物工程重点实验室 贵阳 550025
  • 收稿日期:2020-08-07 修回日期:2020-09-04 发布日期:2020-10-12
  • 通讯作者: 薛伟
  • 作者简介:
    * Corresponding author. E-mail:
  • 基金资助:
    国家自然科学基金(21867003); 贵州省自然科学基金(20192452); 贵州省自然科学基金(20191105); 贵州省自然科学基金(20171028)

Design, Synthesis and Biological Activities of Myricetin Derivatives Containing Quinazoline Thioether Moiety

Jun He1, Xuemei Tang1, Qing Zhou1, Feng Peng1, Tingting Liu1, Liwei Liu1, Ming He1, Chengwei Xie1, Wei Xue1,*()   

  1. 1 Laboratory of Green Pesticide and Bioengineering of Ministry of Education, State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang 550025
  • Received:2020-08-07 Revised:2020-09-04 Published:2020-10-12
  • Contact: Wei Xue
  • Supported by:
    the National Natural Science Foundation of China(21867003); the Natural Science Foundation of Guizhou Province(20192452); the Natural Science Foundation of Guizhou Province(20191105); the Natural Science Foundation of Guizhou Province(20171028)

以杨梅苷为原料, 通过活性拼接, 设计并合成一系列含喹唑啉硫醚的杨梅素衍生物, 其结构通过1H NMR、13C NMR、19F NMR和HRMS进行确证. 生物活性测试结果表明, 该类化合物对水稻白叶枯病菌(X. Oryzae)、柑橘溃疡病菌(X. Citri)和烟草青枯病菌(R. Solanacearum)表现出一定的抑制活性. 其中, 5,7-二甲氧基-3-(3-((6-溴喹唑啉-4-基)硫基)丙氧基)-2-(3,4,5-三甲氧基苯基)-4H-色烯-4-酮(A15)对水稻白叶枯病菌的EC50值为13.9 μg/mL, 优于对照药叶枯唑(88.9 μg/mL)和噻菌铜(68.1 μg/mL); 5,7-二甲氧基-3-(4-((6-氯喹唑啉-4-基)硫基)丁氧基)-2-(3,4,5-三甲氧基苯基)-4H-色烯-4-酮(A3)、5,7-二甲氧基-3-(3-((6-氯喹唑啉-4-基)硫基)丙氧基)-2-(3,4,5-三甲氧基苯基)-4H-色烯-4-酮(A14)、5,7-二甲氧基- 3-(3-((6-溴喹唑啉-4-基)硫基)丙氧基)-2-(3,4,5-三甲氧基苯基)-4H-色烯-4-酮(A15)和5,7-二甲氧基-3-(3-((6-氟喹唑啉-4-基)硫基)丙氧基)-2-(3,4,5-三甲氧基苯基)-4H-色烯-4-酮(A16)对烟草青枯病菌的EC50值分别为1.1, 14.0, 11.9和7.5 μg/mL, 优于对照药叶枯唑(38.5 μg/mL)和噻菌铜(184.8 μg/mL). 活体实验结果表明, 化合物A15对水稻白叶枯病菌的具有良好治疗活性和保护活性. 通过扫描电镜成像初步探讨了目标化合物A3对烟草青枯病菌和A15对水稻白叶枯病菌的抑菌作用机制.

关键词: 杨梅素衍生物, 喹唑啉硫醚, 生物活性, 活体实验, 扫描电镜

A series of myricetin derivatives containing quinazoline thioether moiety were designed and synthesized using myricetrin as the starting material through active splicing strategy. All target compounds were characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. Their biological activities were evaluated. The results of biological activities showed that these compounds exhibited certain inhibitory activities against X. oryzae, X. citri and R. solanacearum. Among them, 3-(3-((6-bro- moquinazolin-4-yl)thio)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A15) displayed appreciable inhibitory effect against X. oryzae with a half maximal effective concentration (EC50) values of 13.9 μg/mL, which was better than those of the control drugs of bismerthiazol (88.9 μg/mL) and thiodiazole-copper (68.1 μg/mL). The EC50 values of 3-(4- ((6-chloroquinazolin-4-yl)thio)butoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A3), 3-(3-((6-chloro- quinazolin-4-yl)thio)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A14), 3-(3-((6-chloroquinazolin- 4-yl)thio)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A15) and 3-(3-((6-fluoroquinazolin-4-yl)- thio)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A16) against Ralstonia solanacearum were 1.1, 14.0, 11.9 and 7.5 μg/mL, respectively, which were superior to the control drugs of bismerthiazol (38.5 μg/mL) and thio-diazole-copper (184.8 μg/mL). The results of in vivo experiments showed that compound A15 has good curative and protective activities against X. oryzae. The possible antibacterial mechanisms of target compound A3 against R. solanacearum and A15 against X. oryzae were preliminarily discussed base on scanning electron microscope analyses.

Key words: myricetin derivative, quinazoline thioether, biological activity, in vivo experiment, scanning electron microscope