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Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone?A.

ABSTRACT: Natural products have historically been a major source of antibiotics and therefore novel scaffolds are constantly of interest. The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone?A, 15 structural analogues to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

SUBMITTER: Mills JJ

PROVIDER: S-EPMC6033662 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A.

Mills Jonathan J JJ Robinson Kaylib R KR Zehnder Troy E TE Pierce Joshua G JG

Angewandte Chemie (International ed. in English) 20180610 28

Natural products have historically been a major source of antibiotics and therefore novel scaffolds are constantly of interest. The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogues t ...[more]

PMID: 29845720

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