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Total Synthesis of Albicidin: A Lead Structure from Xanthomonas albilineans for Potent Antibacterial Gyrase Inhibitors
Author(s) -
Kretz Julian,
Kerwat Dennis,
Schubert Vivien,
Grätz Stefan,
Pesic Alexander,
Semsary Siamak,
Cociancich Stéphane,
Royer Monique,
Süssmuth Roderich D.
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201409584
Subject(s) - dna gyrase , antibacterial activity , xanthomonas , biology , bacteria , antibacterial agent , microbiology and biotechnology , escherichia coli , biochemistry , antibiotics , gene , genetics
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.