Abstract
AbstractMedermycin, produced by Streptomyces species, represents a family of antibiotics with significant activity against Gram-positive pathogens. The biosynthesis of this family of natural products has been studied, and new skeletons related to medermycin have rarely been reported until recently. Herein, we report eight chimeric medermycin-type natural products with unusual polycyclic skeletons. The formation of these compounds features some key nonenzymatic steps, which inspired us to construct complex polycyclic skeletons via three efficient one-step reactions under mild conditions. This strategy was further developed to efficiently synthesize analogues for biological activity studies. The synthetic compounds, chimedermycins L and M, and sekgranaticin B, show potent antibacterial activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and methicillin-resistant Staphylococcus epidermidis. This work paves the way for understanding the nonenzymatic formation of complex natural products and using it to synthesize natural product derivatives.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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