Aim: An urgent need for the development of antibiotics with novel structures and unexploited targets. Materials & methods: Racemic chuangxinmycin was obtained via a novel synthesis route. Chiral preparative chromatography was used to separate chuangxinmycin from its epimers, and four stereoisomers were obtained. Fourteen derivatives were synthesized and their antibacterial activities were evaluated against Escherichia coli and Staphylococcus aureus. Results: Synthesized (3S, 4R)-chuangxinmycin showed antibacterial activity against S. aureus with minimum inhibitory concentration of 4-8 μg/ml (17.2-34.3 μM), which were consistent with the antibacterial activity of chuangxinmycin obtained by fermentation. The minimum inhibitory concentrations of other stereoscopic chuangxinmycin species and chuangxinmycin derivatives were >128 μg/ml. Conclusion: Results indicate that the antibacterial activity of chuangxinmycin is dependent on the stereoselectivity of structures, and that the electron cloud density and amphipathic properties of chuangxinmycin have little effect on its antibacterial activity.
Keywords: antibacterial activity; chuangxinmycin; derivatization; resolution; total synthesis.