3-杂环硫亚甲基头孢菌素衍生物的半合成及抗菌活性研究  

Studies on Semisynthesis and Antibacterial Activity of 3 Heterocyclicthiomethyl Cephalosporins

作　　者：郝兰[1] 惠新平[1] 张自义[1] 管作武[2] 何玉林[3] 于红娟[3] 

机构地区：[1]兰州大学化学化工学院,兰州730000 [2]北京医科大学应用药物研究所,北京100083 [3]兰州医学院微生物研究室,兰州730000

出　　处：《高等学校化学学报》1999年第10期1564-1569,共6页Chemical Journal of Chinese Universities

摘　　要：通过取代噁二唑硫酮、噻二唑硫酮及三唑硫酮分别和头孢菌素母体７－ＡＣＡ 反应， 制得１４种７－氨基－３－杂环硫亚甲基头孢菌素新母体２ａ—２ｎ， 用１－芳基－５－甲基－１Ｈ－１，２，３－三唑－４－甲酰氯与头孢菌素新母体缩合， 制得２ 种新的７β－（１－芳基－５－甲基－１Ｈ－１，２，３－三唑－４－甲酰胺基）－３－（２－取代１，３，４－噁二唑－５－硫亚甲基）头孢菌素４ｃ， ４ｄ． 新化合物结构经元素分析、ＩＲ、１Ｈ ＮＭＲ及ＦＡＢ－ＭＳ确认． 初步体外抗菌结果表明， 新母体化合物２ 对革兰氏阳性菌有抑制活性且在相同浓度下比７－ＡＣＡ强２０ 倍， 而头孢菌素４ｃ， ４ｄFourteen new mother nucleus of 7 amino 3 heterocyclicthiomethyl cephalosporins 2a_2n were synthesized by the reaction of 7 ACA with 2 substituted 1,3,4 oxadiazol 5 thione 1a_1g, 2 arylamino 1,3,4 thiadiazol 5 thione 1h_1l or 1, 2, 4 triazoline 5 thione 1m, 1n. Two new compounds, 7 (1 aryl 5 methyl 1 H 1,2,3 triazol 4 formylamido) 3 (2 substituted 1,3,4 oxadiazol 5 thiomethyl) cephalosporins 4c, 4d, were obtained by the acylation of 7 amino group of 2c, 2d with 1 aryl 5 methyl 1 H 1,2,3 triazol 4 formyl chloride 3a, 3b. The structures of the compounds synthesized were confirmed by elementary analyses, IR, 1H NMR and FAB MS. In preliminary antibacterial sensitivity test, the compounds 2a_2l were found to show higher antibacterial activity than 7 ACA against Gram positive bacteria, 4c, 4d were found to have significant antibacterial activity against both Gram positive and Gram negative bacteria.

关 键 词：头孢菌素 杂环 半合成 抗菌活性 硫亚甲基 

分 类 号：TQ465.1[化学工程—制药化工]