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Epoxy Isonitriles, A Unique Class of Antibiotics: Synthesis of Their Metabolites and Biological Investigations
Author(s) -
Ernouf Guillaume,
Wilt Ingrid K.,
Zahim Sara,
Wuest William M.
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800550
Subject(s) - epoxy , ketone , chemistry , moiety , metabolite , antibacterial activity , epoxide , biological activity , staphylococcus aureus , combinatorial chemistry , organic chemistry , stereochemistry , biochemistry , bacteria , catalysis , biology , in vitro , genetics
Abstract Epoxy isonitrile containing natural products often possess specific and potent antibacterial activity against Gram‐positive pathogens. This scaffold, however, is extremely labile under acidic and basic conditions, undergoing a Payne rearrangement to produce a stable epoxy ketone metabolite and releasing hydrogen cyanide. We synthesized and performed biological assays with epoxy ketone containing metabolites and identified that the epoxy isonitrile moiety is pertinent for biological activity. Serendipitously, we discovered an α,β‐unsaturated epoxy ketone analogue that exhibited moderate activity against Staphylococcus aureus .