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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1HNMR,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.
According to the principle of superposition of biological activity, three series of 12 novel 2/3-substituted thio-5-o-hydroxy groups Phenoxazoles 5a-7d. Methyl salicylate reacts with hydrazine hydrate in ethanol to form salicylic hydrazide, which reacts with carbon disulfide or ammonium thiocyanate and hydrochloric acid to form 5-o-hydroxyphenyl-1,3-dihydroxy- 4-oxadiazole-2-thione (2), 5-o-hydroxyphenyl-1,3,4-thiadiazole-2-thione (3) and 5-o-hydroxyphenyl- 2,4-triazole-3-thione (4), and alkylated with (substituted) haloacetophenone under basic condition to give the target compound.The structure of the target compound was confirmed by 1HNMR, IR and elemental analysis Bacteriostasis test showed that the antibacterial rate of Candida albicans and Escherichia coli was over 92% when the mass concentration was 0.01%, and had strong antibacterial activity. The antibacterial activity against Staphylococcus aureus was over 82% , Indicating that the target compounds have broad-spectrum antibacterial activity against different strains and are a class of highly-potential antifungal and anti-Gram-negative bacterial compounds. The structure-activity analysis shows that the acetophenone ring Substituent Type has a significant impact on the antibacterial activity of the compound, the introduction of Cl, Br, etc. a halogen atom, can significantly enhance the antibacterial activity of the compound, and the power supply into the CH3 group, it can be reduced antibacterial activity.