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有机化学
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有机化学 ›› 2010, Vol. 30 ›› Issue (12): 1914-1920. 上一篇    下一篇

研究简报

2/3-取代硫基-5-邻羟基苯基唑类化合物的合成及抑菌活性

朱姗姗1，卢俊瑞*,1，辛春伟1，卢博为2，鲍秀荣1，唐大伟1，邹敏1，刘倩1   

  1. (1天津理工大学化学化工学院 天津 300384)
    (2南开大学化学学院 天津 300071)
  • 收稿日期:2009-10-27 修回日期:2010-05-07 发布日期:2010-07-05
  • 通讯作者: 卢俊瑞 E-mail:lujunrui@tjut.edu.cn
  • 基金资助:

    国家自然科学基金(Nos. 20776114;20976135)；天津市高校科技发展基金（Nos. 2006ZD33;20050712）

Synthesis and Antibacterial Activities of 2/3-Substituted Sul-fur-5-o-hydroxyphenyl Zoles Compounds

Zhu shanshan1 Lu Junrui*,1 Xin Chun-wei1 Lu Bowei2 Bao Xiurong1 Tang Dawei1 Zou Min1 Liu Qian1   

  1. (1 School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384)
    (2 College of Chemistry, Nankai University, Tian-jin 300071)
  • Received:2009-10-27 Revised:2010-05-07 Published:2010-07-05
  • Contact: Jun-Rui LU E-mail:lujunrui@tjut.edu.cn

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被引次数

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根据生物活性叠加原理, 将“邻羟基苯基”和“唑类杂环”分子片断合理组合, 设计合成了三个系列12种新型2/3-取代硫基-5-邻羟基苯基唑类化合物5a～7d. 水杨酸甲酯在乙醇中与水合肼反应生成水杨酰肼, 水杨酰肼与二硫化碳或硫氰酸铵和盐酸反应, 生成5-邻羟基苯基-1,3,4-噁二唑-2-硫酮(2), 5-邻羟基苯基-1,3,4-噻二唑-2-硫酮(3)和5-邻羟基苯基-4H-1,2,4-三唑-3-硫酮(4), 最后在碱性条件下与(取代)卤代苯乙酮发生烷基化反应生成目标化合物. 目标化合物的结构经1H NMR, IR和元素分析等表征确认. 抑菌测试表明, 质量浓度为0.01%时, 对白色念珠菌、大肠杆菌的抑菌率高达92%以上, 具有强抑菌活性|对金黄色葡萄球菌抑菌率高达82%以上, 具有较强的抑菌活性|这表明目标化合物对不同菌株具有广谱抑菌活性, 是一类极具潜力的抗真菌、抗革兰氏阴性菌化合物. 构效分析表明, 苯乙酮环上取代基的类型对化合物抑菌活性有重要影响, 引入Cl, Br等卤原子, 能显著增强化合物的抑菌活性, 而引入CH3供电基团, 能降低其抑菌活性.

关键词: 2-取代硫基-5-邻羟基苯基-1,3,4-噁二唑, 2-取代硫基-5-邻羟基苯基-1,3,4-噻二唑, 3-取代硫基-5-邻羟基苯基- 1,2,4-三唑, 表征, 抑菌活性

A series of novel 2/3-substituted sulfur-5-o-hydroxyphenyl zoles compounds 5a～7d were designed by means of combining segments o-hydroxyphenyl and azole heterocycles, according to the superpostion principle of reinforcement of biological activities. Salicylic hydrazides were synthesized by methylsalicylate with hydrazinehydrate in ethanol, then, reacted with carbon disulfide or ammonium thiocyanate and hydrochloride to obtain 5-o-hydroxyphenyl-1,3,4-oxadiazole-2-thiones (2), 5-o-hydroxyphenyl-1,3,4- thiadia-zole-2-thiones (3) and 5-o-hydroxyphenyl-4H-1,2,4-triazole-3-thiones (4). Finally, under alkaline conditions, the target compounds were obtained by nucleophilic substi-tution reaction with the halogenated acetophenone. The structures of final products were determined by 1HNMR, IR spectra and element analysis. The result of preliminary bioassay showed that the title compounds had 92% inhibitory rate against Monilia albican and Escherichia coli at 0.01% mass concentration and a favorable extent of antibacterial activities against Staphylococcus aureus (over 82%). This kind of compounds have broad spectrum antibacterial activities against different bacteria and they would be a good choice of antibacterial compounds against fungi and gram-negative bacte-ria. The analysis of structure-activity relationship showed that the antibacterial activities of title compounds were enhanced by the halogen groups, such as Cl and Br, but reduced by electron-donating groups of the phenylethanone rings, such as CH3.

Key words: 2-substituted sulfur-5-o-hydroxyphenyl-1,3,4-oxadiazole, 2-substituted sulfur-5-o-hydroxy- phenyl-1,3,4-thiadiazole, 3-substituted sulfur-5-o-hydroxyphenyl-1,2,4-triazole, characteriza-tion, antibacte- rial activity