Total Synthesis of the Posttranslationally Modified Polyazole Peptide Antibiotic Plantazolicin A

Wada, Hiroki; Williams, Huw E. L.; Moody, Christopher J.

Abstract

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).

Citation

Wada, H., Williams, H. E. L., & Moody, C. J. (2015). Total Synthesis of the Posttranslationally Modified Polyazole Peptide Antibiotic Plantazolicin A. Angewandte Chemie International Edition, 54(50), 15147-15151. https://doi.org/10.1002/anie.201507062

• Journal Article Type: Article
• Acceptance Date: Sep 14, 2015
• Online Publication Date: Oct 16, 2015
• Publication Date: Oct 16, 2015
• Deposit Date: Jul 14, 2016
• Publicly Available Date: Jul 14, 2016
• Journal: Angewandte Chemie International Edition
• Print ISSN: 1433-7851
• Electronic ISSN: 1521-3773
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 54
• Issue: 50
• Pages: 15147-15151
• DOI: https://doi.org/10.1002/anie.201507062
• Keywords: Antibiotics; carbenes; diazo compounds; heterocycles; total synthesis
• Public URL: https://nottingham-repository.worktribe.com/output/763668
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/anie.201507062/abstract
• Additional Information: This is the peer reviewed version of the following article: Wada, H., Williams, H. E. L. and Moody, C. J. (2015), Total Synthesis of the Posttranslationally Modified Polyazole Peptide Antibiotic Plantazolicin A. Angew. Chem. Int. Ed., 54: 15147–15151. doi:10.1002/anie.201507062, which has been published in final form at [http://onlinelibrary.wiley.com/doi/10.1002/anie.201507062/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
• Contract Date: Jul 14, 2016