Tylosin, as one of the important members of 16 membered macrolide antibiotics, has been widely used in the treatment of infectious diseases caused by gram-positive bacteria and mycoplasma, but has little therapeutic effect on infectious diseases caused by gram-negative bacteria and drug-resistant bacteria. At present, one of the purposes modifying tylosin is to expand its antibacterial spectrum. In this paper, using tylosin and its hydrolysate decarbomycin tylosin (desmycosin) and 5-O-mycaminosyltylonolide (OMT) as mother nucleus, 18 new tylosin semisynthetic derivatives were designed and synthesized by modifying the C-20 position, introducing side chain containing 3-quinoline or 3-pyridine, and then their antibacterial activities were evaluated. The target compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. The in vitro anti-sensitive bacteria activity showed that 20-deoxy-20-(N-p-fluorobenzyl-N-(1-(3-quinolyl)-1H-1,2,3-triazol-4-yl)methylamino)-5-O-my- caminosyltylonolide (4g) performed the most prominently. Minimum inhibitory concentration (MIC) values of compound 4g against S. aureus and E. coli were < 0.0625 and 4 μg•mL^–1. The in vitro anti-drug resistant bacteria activity showed that MIC values of compound 4g against S. hemolyticus and E. coli were < 0.0625 and 8 μg•mL^–1. This provides a theoretical basis for further structural optimization and discovery of novel tylosin derivatives with wider antibacterial spectrum and better antibacterial activity.

Key words: tylosin derivatives, 5-O-mycaminosyltylonolide, 3-quinoline, synthesis, antibacterial activity