Synthesis of 9‑Dechlorochrysophaentin A Enables Studies Revealing Bacterial Cell Wall Biosynthesis Inhibition Phenotype in B. subtilis

• Published in: Journal of the American Chemical Society 2020-09, Vol.142 (38), p.16161-16166
• Main Authors: Fullenkamp, Christopher R, Hsu, Yen-Pang, Quardokus, Ellen M, Zhao, Gengxiang, Bewley, Carole A, VanNieuwenhze, Michael, Sulikowski, Gary A
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Bacillus subtilis - drug effects; Biological Products - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; Cell Wall - drug effects; Cell Wall - metabolism; Eukaryota - chemistry; Microbial Sensitivity Tests; Molecular Structure; Phenotype; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.0c04917

Chrysophaentin A is an antimicrobial natural product isolated from the marine alga C. taylori in milligram quantity. Structurally, chrysophaentin A features a macrocyclic biaryl ether core incorporating two trisubstituted chloroalkenes at its periphery. A concise synthesis of iso- and 9-dechloro­chrysophaentin A enabled by a Z-selective ring-closing metathesis (RCM) cyclization followed by an oxygen to carbon ring contraction is described. Fluorescent microscopy studies revealed 9-dechloro­chrysophaentins leads to inhibition of bacterial cell wall biosynthesis by disassembly of key divisome proteins, the cornerstone to bacterial cell wall biosynthesis and division.