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

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-bI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、¹HNMR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,4d对革兰氏阳性和阴性菌都有显著抑制活性.

Studies on Semisynthesis and Antibacterial Activity of 3-Heterocyclicthiomethyl Cephalosporins

Fourteen 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.