噻吩磺酰胺类膦酸酯衍生物的合成与生物活性研究  

Synthesis and Bioactivity of Novel Phosphonate Derivatives Containing Thiophene and Sulfonamide Group

作　　者：杨家强 雷延燕 杨红 鄢伯钰 YANG Jia-qiang;LEI Yan-yan;YANG Hong;YAN Bo-yu(School of Pharmacy,Zunyi Medical University,Zunyi 563003,China)

机构地区：[1]遵义医科大学药学院

出　　处：《中国药学杂志》2019年第24期2055-2059,共5页Chinese Pharmaceutical Journal

基　　金：贵州省科技厅国际合作项目资助(黔科合外G字[2014]7013);贵州省中医药管理局中医药、民族医药科学技术研究项目资助(QZYY[2018]085);遵义市汇川区科技局资助项目资助(E-123)

摘　　要：目的为了寻找抗菌候选化合物,一系列噻吩磺酰胺类膦酸酯衍生物被设计合成。方法首先,以芳香醛、醋酸铵、亚磷酸二乙酯和Al(OTf)3为反应原料,采用无溶剂一锅法制备中间体Ⅰ;然后,在碱性离子液体[Bmim]OH条件下,中间体Ⅰ与磺酰氯反应制备目标化合物;并采用两倍稀释法对目标物进行体外抗菌活性测试。结果合成了12个目标化合物,经1H-NMR、13C-NMR和MS确认结构;抗菌活性测试结果显示,该类衍生物对所测革兰阳性菌和革兰阴性菌均有不同程度的抑制活性,尤以目标物Ⅱe、Ⅱk的抗菌活性最为突出,其中前者对金黄色葡萄球菌(S.aureus)、大肠埃希菌(E.coli)、耐甲氧西林金黄色葡萄球菌(MRSA)及耐氟喹诺酮类大肠杆菌(MREC)的MIC分别为32、64、32和128μg·m L^-1,后者对S. aureus、E.coli、MRSA及MREC的MIC分别为16、64、32和64μg·m L^-1,抗菌活性明显优于对照药磺胺嘧啶,接近于对照药加替沙星。结论该类衍生物具有潜在的抗菌活性,值得进一步结构优化和深入研究。OBJECTIVE To design and synthsize a series of novel phosphonate derivatives. METHODS First,the intermediates of aminophosphonate was prepared by solvent-free one-pot method using aromatic aldehyde,ammonium acetate,diethyl phosphite and Al( OTf)3 as raw materials. Then,using basic ionic liquid [Bmim]OH as catalyst,the target compounds were synthesized by the reaction of intermediate with sulfonyl chloride. And the antibacterial activities of the products were evaluated by the agar dilution method. RESULTS Twelve title compounds were synthesized,and their structures were clearly established by1 H-NMR,13 C-NMR and MS. The results showed that the derivatives have different inhibitory activities against Gram-positive bacteria and Gram-negative bacteria,especially the compounds Ⅱe and Ⅱk showed better activity,the MIC of the former for S. aureus,E. coli,MRSA and MREC was 32,64,32,and 128 μg·mL-1,respectively,and the MIC of the latter was 16,64,32,and 64 μg·mL-1,respectively. Its antibacterial activities were significantly better than that of the control drug sulfadiazine,and close to that of gatifloxacin.CONCLUSION These derivatives have potential antibacterial activity,which is worth for further structural optimization and study.

关 键 词：磺胺 噻吩 膦酸酯 合成 抗菌活性 

分 类 号：R914[医药卫生—药物化学] R965[医药卫生—药学]