title: Total synthesis of albicidin: a lead structure from Xanthomonas albilineans for potent antibacterial gyrase inhibitors.
abstract: The peptide antibiotic albicidin, which is synthesized by the plant pathogenic bacterium Xanthomonas albilineans, displays remarkable antibacterial activity against various Gram-positive and Gram-negative microorganisms. The low amounts of albicidin obtainable from the producing organism or through heterologous expression are limiting factors in providing sufficient material for bioactivity profiling and structure-activity studies. Therefore, we developed a convergent total synthesis route toward albicidin. The unexpectedly difficult formation of amide bonds between the aromatic amino acids was achieved through a triphosgene-mediated coupling strategy. The herein presented synthesis of albicidin confirms the previously determined chemical structure and underlines the extraordinary antibacterial activity of this compound. The synthetic protocol will provide multigram amounts of albicidin for further profiling of its drug properties.
authors.affiliation: Institut für Organische Chemie, Technische Universität Berlin, Straße des 17 Juni 124, 10623 Berlin (Germany) http://www.biochemie.tu-berlin.de.
authors.forename: Julian
authors.initials: J
authors.lastname: Kretz
authors.forename: Dennis
authors.initials: D
authors.lastname: Kerwat
authors.forename: Vivien
authors.initials: V
authors.lastname: Schubert
authors.forename: Stefan
authors.initials: S
authors.lastname: Grätz
authors.forename: Alexander
authors.initials: A
authors.lastname: Pesic
authors.forename: Siamak
authors.initials: S
authors.lastname: Semsary
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cociancich
authors.forename: Monique
authors.initials: M
authors.lastname: Royer
authors.forename: Roderich D
authors.initials: RD
authors.lastname: Süssmuth
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D027081:DNA Gyrase / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009930:Organic Chemicals / Q000737:chemistry / Q000494:pharmacology; D014974:Xanthomonas / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D009930:Organic Chemicals; C046156:albicidin; D027081:DNA Gyrase
keywords: albicidin; gyrase; para-aminobenzoic acid; peptides; total synthesis