Total synthesis of the post-translationally modified polyazole peptide antibiotic plantazolicin A

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...

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Main Authors: Wada, Hiroki, Williams, Huw E. L., Moody, Christopher J.
Format: Article
Published: Wiley-VCH Verlag 2015
Subjects:
Online Access:https://eprints.nottingham.ac.uk/34953/
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author Wada, Hiroki
Williams, Huw E. L.
Moody, Christopher J.
author_facet Wada, Hiroki
Williams, Huw E. L.
Moody, Christopher J.
author_sort Wada, Hiroki
building Nottingham Research Data Repository
collection Online Access
description 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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spelling nottingham-349532020-05-04T17:19:23Z https://eprints.nottingham.ac.uk/34953/ Total synthesis of the post-translationally modified polyazole peptide antibiotic plantazolicin A Wada, Hiroki Williams, Huw E. L. Moody, Christopher J. 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). Wiley-VCH Verlag 2015-10-16 Article PeerReviewed Wada, Hiroki, 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 Antibiotics; carbenes; diazo compounds; heterocycles; total synthesis http://onlinelibrary.wiley.com/doi/10.1002/anie.201507062/abstract doi:10.1002/anie.201507062 doi:10.1002/anie.201507062
spellingShingle Antibiotics; carbenes; diazo compounds; heterocycles; total synthesis
Wada, Hiroki
Williams, Huw E. L.
Moody, Christopher J.
Total synthesis of the post-translationally modified polyazole peptide antibiotic plantazolicin A
title Total synthesis of the post-translationally modified polyazole peptide antibiotic plantazolicin A
title_full Total synthesis of the post-translationally modified polyazole peptide antibiotic plantazolicin A
title_fullStr Total synthesis of the post-translationally modified polyazole peptide antibiotic plantazolicin A
title_full_unstemmed Total synthesis of the post-translationally modified polyazole peptide antibiotic plantazolicin A
title_short Total synthesis of the post-translationally modified polyazole peptide antibiotic plantazolicin A
title_sort total synthesis of the post-translationally modified polyazole peptide antibiotic plantazolicin a
topic Antibiotics; carbenes; diazo compounds; heterocycles; total synthesis
url https://eprints.nottingham.ac.uk/34953/
https://eprints.nottingham.ac.uk/34953/
https://eprints.nottingham.ac.uk/34953/