Synthesis and antibacterial activities of acylide derivatives bearing an aryl-tetrazolyl chain

Ling-Xing Shan,1 Ping-Hua Sun,1,2 Bao-Qin Guo,1 Xing-Jun Xu,1 Zhi-Qiang Li,1 Jia-Zhi Sun,2 Shu-Feng Zhou,2 Wei-Min Chen1 1Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, People's Republic of China; 2College of Pharmacy, University of South Florida, Tampa, FL, USA Abstract: Seventeen acylides bearing an aryl-tetrazolyl alkyl-substituted side chain were synthesized, starting from clarithromycin, via several reactions including hydrolysis, acetylating, esterification, carbamylation, and Michael addition. The structures of all new compounds were confirmed by 1H nuclear magnetic resonance spectroscopy, 13C nuclear magnetic resonance spectroscopy, and mass spectrometry. All these synthesized acylides were evaluated for in vitro antimicrobial activities against gram-positive pathogens (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative pathogens (Pseudomonas aeruginosa, Escherichia coli), using the broth microdilution method. Results showed that compounds 10e, 10f, 10g, 10 h, 10o have good antibacterial activities. Keywords: acylide, clarithromycin, synthesis, antibacterial activity