2-位亚甲基头孢类抗生素的设计、合成与生物活性

Design, synthesis and bioactivity of 2-methylene-cephalosporin antibiotics

目的设计合成具有抗菌活性的2-位亚甲基头孢类抗生素。方法以7-苯乙酰氨基-3-氯甲基-头孢-3-烯-4-羧酸对甲氧基苄酯(GCLE)为起始原料,经Mannich反应、酶解、缩合等反应制得2-位亚甲基头孢类抗生素。通过微量稀释法测定了其对标准金黄色葡萄球菌、标准肺炎克雷伯杆菌的最小抑菌浓度。结果合成了4个新化合物8a～8d,利用1H-NMR和MS确证了结构,初步测试显示较好的抗菌活性。结论初步生物活性试验结果显示化合物8a、8b和8d对标准金黄色葡萄球菌的抗菌活性均与头孢克肟和头孢地尼相当,化合物8a、8b对标准肺炎克雷伯杆菌的抗菌活性与头孢克肟和头孢地尼相当。

Objective To design and synthesize 2-methylene-cephalosporin antibiotics for antibacterial activity. Methods 2-methylene- cephalosporin antibiotics were synthesized from the starting material GCLE via Mannich reaction, enzymolysis, and condensation, etc. The study on antibacterial activity was carried out using micro-dilution to detect the minimum inhibitory concentrations （MIC） on standard Staphylococcus aureus and standard Bacillus canalis capsulatus. Results The four novel compounds were synthesized. All the compounds were characterized by 1 H-NMR and MS. The preliminary test showed that the compound had good antibacterial activities. Conclusion Through the preliminary bioactivity test, the results show that the antibacterial activities of the compounds 8a, 8b, and 8d on standard Staphylococcus aureus are the same to those of cefixime and cefdinir, and the antibacterial activities of the compounds 8a and 8b on standard Bacillus canalis capsulatus are the same to those of cefixime and cefdinir.