Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A

Angewandte Chemie
Jonathan J MillsJoshua G Pierce

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.

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Citations

Nov 7, 2019·Chembiochem : a European Journal of Chemical Biology·Bram H FrohockJoshua G Pierce
Feb 7, 2020·Natural Product Reports·Anthony R CarrollMichèle R Prinsep
Aug 10, 2020·Applied and Environmental Microbiology·K F GriewischJ R Elfenbein
Mar 19, 2021·Accounts of Chemical Research·M Alejandro Valdes-PenaJoshua G Pierce
Sep 29, 2020·The Journal of Organic Chemistry·Kuan ZhengRan Hong

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