title: Total Synthesis of the Posttranslationally Modified Polyazole Peptide Antibiotic Plantazolicin A.
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 posttranslational 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).
authors.affiliation: School of Chemistry, University of Nottingham, Nottingham NG7 2RD (UK).
authors.forename: Hiroki
authors.initials: H
authors.lastname: Wada
authors.affiliation: School of Chemistry, University of Nottingham, Nottingham NG7 2RD (UK).
authors.forename: Huw E L
authors.initials: HE
authors.lastname: Williams
authors.affiliation: School of Chemistry, University of Nottingham, Nottingham NG7 2RD (UK). c.j.moody@nottingham.ac.uk.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Moody
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001393:Azoles / Q000737:chemistry* / Q000494:pharmacology; D002384:Catalysis; D004305:Dose-Response Relationship, Drug; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D012238:Rhodium / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001393:Azoles; D009842:Oligopeptides; D011108:Polymers; C560834:plantazolicin A; C030011:carbene; D012238:Rhodium; D008697:Methane
keywords: antibiotics; carbenes; diazo compounds; heterocycles; total synthesis