SIOC English
有机化学
高级检索

有机化学 >

2019 , Vol. 39 >Issue 10: 2965 - 2972

DOI: https://doi.org/10.6023/cjoc201903031

研究简报

新型哌啶基肉桂醛缩氨基硫脲衍生物的设计、合成及抑菌活性研究

  • 张学博 ,
  • 马航宇 ,
  • 孙腾达 ,
  • 雷鹏 ,
  • 杨新玲 ,
  • 张晓鸣 ,
  • 凌云
展开
  • 中国农业大学理学院 应用化学系 北京 100193

收稿日期: 2019-03-17

  修回日期: 2019-04-18

  网络出版日期: 2019-05-21

基金资助

国家自然科学基金(No. 21672258)

收起

Design, Synthesis and Fungicidal Activity of Novel Piperidine Containing Cinnamaldehyde Thiosemicarbazide Derivatives

  • Xuebo Zhang, ,
  • Hangyu Ma, ,
  • Tengda Sun, ,
  • Peng Lei, ,
  • Xinling Yang, ,
  • Xiaoming Zhang, ,
  • Yun Ling,
Expand
  • Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193

Received date: 2019-03-17

  Revised date: 2019-04-18

  Online published: 2019-05-21

Supported by

Project supported by the National Natural Science Foundation of China(No. 21672258)

Fold

摘要

为了发现高活性杀菌剂先导化合物, 利用骨架跃迁原理, 以哌啶基苯甲醛缩氨基硫脲为先导化合物, 设计并合成了一系列未见文献报道的肉桂醛缩氨基硫脲类衍生物. 化合物结构经过 1H NMR、 13C NMR、IR、元素分析或HRMS确证. 离体抑菌活性测试结果表明, 一些化合物对多种病原真菌表现出优异的杀菌活性. 在50 μg/mL浓度下, N'-[(1E, 2E)-3-(4-氯苯基)烯丙基]哌啶-1-硫代酰肼(3a)和N'-((1E,2E)-3-苯基烯丙基)哌啶-1-硫代酰肼(3p)对苹果腐烂病菌、油菜菌核病菌菌、瓜果腐霉病菌和水稻纹枯病菌的离体抑菌活性均在95%以上. EC50测试结果表明, 化合物3a, 3p对这4种病原真菌EC50均在10 μg/mL以内, 表现出广谱的杀菌活性. 初步构效关系分析表明, 将苯甲醛骨架替换为具有杀菌活性的肉桂醛骨架结构, 有利于活性的提高.

关键词： 天然产物; 肉桂醛; 缩氨基硫脲; 合成; 杀菌活性

本文引用格式

张学博 , 马航宇 , 孙腾达 , 雷鹏 , 杨新玲 , 张晓鸣 , 凌云 . 新型哌啶基肉桂醛缩氨基硫脲衍生物的设计、合成及抑菌活性研究[J]. 有机化学, 2019 , 39(10) : 2965 -2972 . DOI: 10.6023/cjoc201903031

Abstract

In order to find new lead compound with higher fungicidal activity, a series of novel cinnamaldehyde thio- semicarbazone derivatives were designed and synthesized according to scaffold hopping strategy, based on the lead of the thiosemicarbazide derivatives containing piperidine discovered in our preliminary studies. Their structures were confirmed by 1H NMR, 13C NMR, IR, elemental analysis or HRMS. The bioassay results indicated that some compounds exhibited excellent fungicidal activities. In particular, N'-((1E,2E)-3-(4-chlorophenyl)allylidene)piperidine-1-carbothiohydrazide (3a) and N'-((1E, 2E)-3-phenylallylidene)piperidine-1-carbothiohydrazide (3p) showed above 95% inhibitory rate against Cytospora sp, S. sclerotiorum, P. aphanidermatum and T. cucumeris at 50 μg/mL with EC50 values lower than 10 μg/mL. The preliminary structure-activity relationship indicated that cinnamaldehyde contributes more to the bioactivity than benzaldehyde.

Key words： natural product; cinnamyl aldehyde; thiosemicarbazide; synthesis; fungicidal activity

参考文献

[1] Godfray, H. C. J.; Beddington, J. R.; Crute, I. R.; Haddad, L.; Lawrence, D.; Muir, J. F.; Pretty, J.; Robinson, S.; Thomas, S. M.; Toulmin, C . Science 2010, 327, 812.
[2] Gerwick, B. C.; Sparks, T. C. Pest Manage. Sci. 2014, 70, 1169.
[3] Balba, H. J. Environ. Sci. Health, Part B 2007, 42, 441.
[4] Sparks, T. C.; Hahn, D. R.; Garizi, N. V. Pest Manage. Sci. 2017, 73, 700.
[5] Ashakirin, S. N.; Tripathy, M.; Patil, U. K.; Abdul Majeed, A. B. Int. J. Pharm. Sci. Res. 2017, 8, 2333.
[6] Ka, H.; Park, H. J.; Jung, H. J.; Choi, J. W.; Cho, K. S.; Ha, J.; Lee, K. T. Cancer Lett. 2003, 196, 143.
[7] Chang, S. T.; Chen, P. F.; Chang, S. C. J. Ethnopharmacol. 2001, 77, 123.
[8] Zhu, Y. J.; Song, K. K.; Li, Z. C.; Pan, Z. Z.; Guo, Y. J.; Zhou, J. J.; Wang, Q.; Liu, B.; Chen, Q. X. J. Agric. Food Chem. 2009, 57, 5518.
[9] Gutiérrez, L.; Escudero, A.; Batlle, R.; Nerín, C. J. Agric. Food Chem. 2009, 57, 8564.
[10] Du, W. X.; Avena-Bustillos, R. J.; Woods, R.; Breksa, A. P.; McHugh, T. H.; Friedman, M.; Levin, C. E.; Mandrell, R. J. Agric. Food Chem. 2012, 60, 7799.
[11] Niknahad, H.; Shuhendler, A.; Galati, G.; Siraki, A. G.; Easson, E.; Poon, R.; O'Brien, P. J. Chem. Biol. Interact. 2003, 143, 119.
[12] Cheng, S. S.; Liu, J. Y.; Tsai, K. H.; Chen, W. J.; Chang, S. T. J. Agric. Food Chem. 2004, 52, 4395.
[13] Yu, Y.; Kalinowski, D. S.; Kovacevic, Z.; Siafakas, A. R.; Jansson, P. J.; Stefani, C.; Lovejoy, D. B.; Sharpe, P. C.; Bernhardt, P. V.; Richardson, D. R. J. Med. Chem. 2009, 52, 5271.
[14] Dong, H.; Liu, J.; Liu, X.; Yu, Y.; Cao, S. J. Mol. Struct. 2018, 1151, 353.
[15] Dong, H.; Liu, J.; Liu, X.; Yu, Y.; Cao, S . Bioorg. Chem. 2017, 75, 106.
[16] Liu, L. F.; Li, P. Y.; Qian, Q. Q.; Lei, X. L.; Huang, Y. X. Chin. J. Org. Chem. 2013, 33, 854 (in Chinese).
[16] ( 刘利锋, 李培源, 钱全全, 雷晓琳, 黄钰湘, 周泉, 黄珊, 肖琦, 苏炜, 有机化学, 2013, 33, 854.)
[17] Xu, Y.; Wang, Z.; Dong, W.; Xing, J.; Liang, P.; Yang, X. L. Chin. J. Org. Chem. 2012, 32, 1278 (in Chinese).
[17] ( 徐焱, 王振, 凌云, 董玮, 邢静, 梁沛, 杨新玲, 有机化学, 2012, 32, 1278.)
[18] Zhang, X. B.; Lei, P.; Sun, T. D; Jin, X. Y.; Yang, X. L.; Ling, Y . Molecules 2017, 22, 2085.
[19] Zhang, X. M.; Lei, P.; Li, X. L.; Yang, X. L.; Zhang, X. B.; Sun, T. D.; Ling, Y. Chin. J. Org. Chem. 2019, 39, 3197 (in Chinese).
[19] ( 张晓鸣, 雷鹏, 李欣潞, 杨新玲, 张学博, 孙腾达, 凌云, 有机化学, 2019, 39, 3197.)
Options
文章导航

/

〈 〉