有机化学 ›› 2013, Vol. 33 ›› Issue (05): 1062-1068.DOI: 10.6023/cjoc201211043 上一篇    下一篇

研究论文

新型5-甲基-1,2,4-三唑-3-硫酮类化合物的合成及抗菌活性研究

戢丹, 卢俊瑞, 辛春伟, 彭春勇, 穆江蓓, 李建发   

  1. 天津理工大学化学化工学院 天津 300384
  • 收稿日期:2012-11-26 修回日期:2012-12-22 出版日期:2013-05-25 发布日期:2013-01-07
  • 通讯作者: 卢俊瑞,lujunrui@tjut.edu.cn E-mail:lujunrui@tjut.edu.cn
  • 基金资助:

    国家自然科学基金(Nos. 21176194, 20976135)和天津市高校科技发展基金(No. 2006ZD33)资助项目.

Synthesis and Biological Activities of Novel 5-Methyl-1,2,4-triazoles-3-thione

Ji Dan, Lu Junrui, Xin Chunwei, Peng Chunyong, Mu Jiangbei, Li Jianfa   

  1. School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384
  • Received:2012-11-26 Revised:2012-12-22 Online:2013-05-25 Published:2013-01-07
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21176194, 20976135), and the Key Project of Tianjin Municipal Science and Technology Commission (No. 2006ZD33).

利用生物活性叠加原理, 以4-氨基-5-甲基-1,2,4-三唑-3-硫酮为原料, 设计合成了15个未见报道的化合物2-N-2',3',4',6'-四-O-乙酰基-β-D-吡喃葡萄糖基-4-N-取代苯基亚胺基-5-甲基-1,2,4-三唑(2a2e), 4-N-取代苄基氨基-5-甲基-1,2,4-三唑(3a3e)和2-N-2',3',4',6'-四-O-乙酰基-β-D-吡喃葡萄糖基-4-N-取代苄基氨基-5-甲基-1,2,4-三唑(4a4e). 其结构经IR, 1H NMR, 13C NMR和元素分析确认. 生物活性测试表明, 所有化合物均表现出一定的抑菌活性, 尤其是化合物4b对大肠杆菌和金黄色葡萄球菌的最小抑菌浓度为8 μg/mL, 明显优于市售抗菌药物氟康唑, 表现出较强的抗细菌活性; 同时, 与三氯生相比, 所有化合物对白色念珠菌的最小抑菌浓度(MIC)均小于或等于32 μg/mL, 亦表现出较好的抗真菌活性.

关键词: 2',3',4',6'-四-O-乙酰基-α-D-吡喃葡萄糖, 1,2,4-三唑, 合成, 表征, 抗菌活性

In this paper, 15 new compounds of 2-N-2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl-4-(N-substituted-phenyl)- imino-5-methyl-1,2,4-triazoles (2a2e), 4-(N-substituted-phenyl)imino-5-methyl-1,2,4-triazole-3-thiones (3a3e) and 2-N-2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl-4-(N-substituted-phenyl)imino-5-methyl-1,2,4-triazoles (4a4e) were rationally designed and synthesized according to the principle of superposition of bioactive substructures by the combination of 1,2,4-triazole, Schiff base and glucosides. Firstly, the Schiff base 4-arylideneamino-1,2,4-triazole-3-thiones (1a1e) has been obtained by the reaction of 4-amino-1,2,4-triazole-3-thiones with substituted salicyladehyde in weak acidic conditions. Then the target compounds 2a2e were prepared from 4-arylideneamino-1,2,4-triazole-3-thiones with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in the presence of potassium hydroxide. The structures of target compounds have been characterized by 1H NMR, 13C NMR, IR and elemental analysis. The results of preliminary bioassay showed that most of the tested compounds displayed variable inhibitory activity. Especially, compounds 4b exhibited much higher activities against Escherichia coli and Staphylococcus aureus than commercial fungicide fluconazole with minimum inhibitory concentration (MIC) values of 16 μg/mL. All of the compounds showed excellent activity against fungal strains with MIC values of 16 μg/mL, which were more effective against Monilia albican than the reference drug triclosan.

Key words: 2',3',4',6'-tetra-O-acetyl-α-D-glucopyranosyl, 1,2,4-triazole, systhesis, antibacterial activity