Total synthesis of the post-translationally modified polyazole peptide antibiotic plantazolicin A
Wada, Hiroki and Williams, Huw E. L. and Moody, Christopher J. (2015) Total synthesis of the post-translationally modified polyazole peptide antibiotic plantazolicin A. Angewandte Chemie International Edition, 54 (50). pp. 15147-15151. ISSN 1433-7851
The power of rhodium carbene methodology in chemistry is demonstrated by the synthesis of a structurally complex polyazole antibiotic. Plantazolicin A, a novel soil bacterium metabolite, comprises a linear array of 10 five-membered rings in two pentacyclic regions that derive from ribosomal peptide synthesis followed by extensive post-translational modification. The compound possesses potent antimicrobial activity, and is selectively active against the anthrax causing organism. A conceptually different synthesis of plantazolicin A is reported in which the key steps are the use of rhodium(II)-catalyzed reactions of diazocarbonyl compounds to generate up to six of the seven oxazole rings of the antibiotic. NMR Spectroscopic studies and molecular modeling, reveal a likely dynamic hairpin conformation with a hinge region around the two isoleucine residues.The compound has modest activity against methicillin-resistant Staphylococcus aureus (MRSA).
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