Search

Medermycin, 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. Nonenzymatic reactions play an important part in the formation of some natural products possessing complex skeletons. Here, the authors report the discovery of eight chimeric medermycin-type natural products and their nonenzymatic construction. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Five new pyrrolizidine alkaloids, bohemamines J—N (1—5), were isolated from Streptomyces sp. CPCC 200497. Their structures were assigned based on detailed spectroscopic analysis and semisynthesis. Bohemamine J (1) possesses a new chimeric skeleton derived from bohemamine A (6) and phenylacetaldehyde. Inspired by the nonenzymatic formation mechanism of the methylene‐bridged dimers isolated from this strain, we synthesized a series of chimeric derivatives (8, 9, and 12—23) through natural product chimera strategy. Compounds 13, 15, 19, and 21 showed significant antioxidant activity. [ABSTRACT FROM AUTHOR]