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Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A
Author(s) -
Mills Jonathan J.,
Robinson Kaylib R.,
Zehnder Troy E.,
Pierce Joshua G.
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201805078
Subject(s) - pharmacophore , natural product , antimicrobial , combinatorial chemistry , chemistry , lipophilicity , biochemical engineering , mechanism (biology) , nanotechnology , stereochemistry , organic chemistry , materials science , engineering , philosophy , epistemology
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.