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Synthesis of Tetramic Acid Fragments Derived from Vancoresmycin Showing Inhibitory Effects towards S. aureus.

ABSTRACT: An efficient route to various vancoresmycin-type tetramic acids has been developed. The modular route is based on an effective Fries-type rearrangement to introduce various appending acetyl residues. The minimum inhibitory concentration (MIC) values of the new tetramic acids against Staphylococcus aureus and Escherichia coli were determined, revealing that three of the new compounds exhibit antimicrobial activity against S. aureus. These bioactive compounds were structurally most closely related to the authentic vancoresmycin building block. Additionally, the compounds induced a lial-lux bioreporter, which responds to cell wall stress induced by antibiotics that interfere with the lipid II biosynthesis cycle. These data suggest the tetramic acid moiety to be a part of the vancoresmycin pharmacophore.

SUBMITTER: Wingen LM

PROVIDER: S-EPMC7496136 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Synthesis of Tetramic Acid Fragments Derived from Vancoresmycin Showing Inhibitory Effects towards S. aureus.

Wingen Lukas Martin LM Rausch Marvin M Schneider Tanja T Menche Dirk D

ChemMedChem 20200626 15

An efficient route to various vancoresmycin-type tetramic acids has been developed. The modular route is based on an effective Fries-type rearrangement to introduce various appending acetyl residues. The minimum inhibitory concentration (MIC) values of the new tetramic acids against Staphylococcus aureus and Escherichia coli were determined, revealing that three of the new compounds exhibit antimicrobial activity against S. aureus. These bioactive compounds were structurally most closely related ...[more]

PMID: 32497343

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