有机化学 ›› 2015, Vol. 35 ›› Issue (4): 858-864.DOI: 10.6023/cjoc201410021 上一篇    下一篇

研究论文

新型S-β-D-葡萄糖苷-1,2,4-三唑的合成及其抗菌活性研究

张瑞波, 卢俊瑞, 辛春伟, 刘金彪, 穆江蓓, 杨旭云, 王宏韫, 王美君, 张贺   

  1. 天津理工大学化学化工学院 天津 300384
  • 收稿日期:2014-10-15 修回日期:2014-11-19 发布日期:2014-12-09
  • 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. 21176194, 21476174)资助项目.

Synthesis and Antibacterial Activities of Novel S-β-D-Glucosides of 1,2,4-Triazole

Zhang Ruibo, Lu Junrui, Xin Chunwei, Liu Jinbiao, Mu Jiangbei, Yang Xuyun, Wang Hongyun, Wang Meijun, Zhang He   

  1. School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384
  • Received:2014-10-15 Revised:2014-11-19 Published:2014-12-09
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21176194, 21476174).

在氢氧化钾溶液中, 取代苯甲酰肼2与CS2生成钾盐3, 然后3在水合肼作用下经过环化, 得到3-巯基-4-氨基-5-取代芳基-1,2,4三唑(4), 在氢氧化钾的丙酮溶液中, 与溴代乙酰化α-D-吡喃型葡萄糖反应合成了9个3-S-2',3',4',6'-四-O-乙酰基-β-D-吡喃葡萄糖基-4-氨基-5-取代苯基-1,2,4-三唑(5a5i). 其结构经1H NMR, 13C NMR, IR和HRMS确认. 对目标化合物进行生物活性测试表明, 对大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌和白色念珠菌均显示了较好的抑菌活性, 其中化合物5g对大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌和白色念珠菌的最小抑菌浓度分别为8, 16, 64, 2 μg/mL, 效果接近或优于对照药物(三氯生、氟康唑)的抑菌效能, 表现出较强的抑菌活性. 利用Autodock Vina程序研究了目标化合物(5a5i)与大肠杆菌FabI受体蛋白分子的相互作用和结合自由能变化规律.

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

A series potassiums 3 were prepared by substituted benzoyl hydrazide 2 and CS2 in potassium hydroxide. These compounds 3 were converted to 4-amino-5-substituted phenyl-3-ylsulfanyl-4H-1,2,4-triazols (4) by cyclization in hydrazine hydrate. Nine novel S-β-D-glucosides (5a5i) were synthesized by glycosylation of 4 and bromo-2,3,4,6-tetra-O-acetyl- α-D-glucopyranoside in the presence of potassium hydroxide with acetone as solvent. The structures of all target compounds were confirmed by 1H NMR, 13C NMR, IR and HRMS spectrum. The results of preliminary bioassay show that most of the tested compounds displayed variable inhibitory activity against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Monilia albican. Especially, compound 5g has strong antibacterial activity with minimum inhibitory concentration values of 8, 16, 64, 2 μg/mL against four tested strains respectively which are similar to or higher than those of the controlled drug fluconazole or triclosan. The interaction and binding free energy of the target compounds 5a5i with FabI were studied by Autodock Vina.

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