新型螺嘧啶三酮类化合物的合成及其抗菌活性  

Synthesis and Antibacterial Activities of Novel Spiropyrimidinetrione Compounds

作　　者：张银勇[1,2] 石程辉 周先礼[1] 

机构地区：[1]西南交通大学生命科学与工程学院,四川成都610031 [2]中国科学院上海药物研究所,上海201203

出　　处：《合成化学》2016年第8期653-662,共10页Chinese Journal of Synthetic Chemistry

摘　　要：根据生物电子等排原理,以2,3,4-三氟苯甲酸为原料,经硝化、还原、氧化和亲核取代反应制得中间体2-(2,3,4-三氟-5-硝基苯)-1,3-二氧戊环(4);4分别经7步反应合成了12个新型的苯并噁唑酮或苯并咪唑酮螺嘧啶三酮类化合物(12a^12f,19a^19f),其结构经1H NMR,13C NMR和ESI-MS表征。采用CLSI标准研究了12和19对甲氧西林耐药金黄色葡萄球菌(A)、甲氧西林耐药表皮葡萄球菌(B)、青霉素耐药肺炎链球菌(C)和化脓性链球菌(D)的体外抗菌活性。结果表明:12的抗菌活性优于19,其中12a的抗菌活性最好,对A^D的MIC值分别为8~16μg·m L^(-1)。According to the principle of bioisosteric, an intermediate[2-（2,3,4-trifluoro-5-nitroben-zene）-1,3-dioxolame（4）] was prepared by the reaction of nitration, reduction, oxidation and nucleo-philic substitution from 2,3,4-trifluorobenzoic acid.Twelve novel spiropyrimidinetrione compounds containing benzoxazolinone or benzimidazolone（12a^12f, 19a^19f） were synthesized by a seven-step reaction from 4.The structures were characterized by 1 H NMR, 13 C NMR and ESI-MS.The anti-bacterial activities of 12 and 19 against methicillin-resistant Ataphylococcus aureus（ A） , methicillin-re-sistant Staphylococcus epidermidis（ B） , penicillin-resistant Streptococcus pneumonia（ C） and Streptococ-cus pyogenes（ D） were investigated by CLSI standard.The results indicated that the antibacterial activi-ties of 12 were better than 19.12a exhibited best activities with MIC of 8~16 μg· mL-1 .

关 键 词：螺嘧啶三酮 苯并噁唑酮 苯并咪唑酮 Ⅱ型拓扑异构酶抑制剂 合成 抗菌活性 

分 类 号：O626.24[理学—有机化学] O626.41[理学—化学]