Diverted Total Synthesis of the Baulamycins and Analogues Reveals an Alternate Mechanism of Action

• Type of Material: Article
• Authors: Andrew D. Steele, Emory University; Guillaume Ernouf, Emory University; Young Eun Lee, Temple University; William Wuest, Emory University
• Language: English
• Date: 2018-02-16
• Publisher: American Chemical Society
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 American Chemical Society.
• Final Published Version (URL): http://dx.doi.org/10.1021/acs.orglett.8b00054
• Title of Journal or Parent Work: Organic Letters
• ISSN: 1523-7060
• Volume: 20
• Issue: 4
• Start Page: 1126
• End Page: 1129
• Grant/Funding Information: This work was supported by the National Institute of General Medical Sciences (GM119426) and the National Science Foundation (CHE1755698).; The NMR instruments used in this work were supported by the National Science Foundation (CHE1531620).
• Keywords: Physical Sciences; SIDEROPHORE BIOSYNTHESIS; Science & Technology; SYNERGY; Chemistry, Organic; ANTIBIOTICS; RESISTANCE; DISCOVERY; COMPUTATION; NATURAL-PRODUCTS; INHIBITORS; IRON; Chemistry
• Research Categories: Health Sciences, Immunology; Chemistry, Organic; Biology, Cell

Abstract

The baulamycins were identified as in vitro siderophore biosynthesis inhibitors. Diverted total synthesis was used to construct the natural products and eight strategic analogues, three of which had improved inhibitory activity. Biological testing then revealed that membrane damage is the predominant mode of action in Staphylococcus aureus cells.