title: Synthesis and biological evaluation of potential threonine synthase inhibitors: Rhizocticin A and Plumbemycin A.
abstract: Rhizocticins and Plumbemycins are natural phosphonate antibiotics produced by the bacterial strains Bacillus subtilis ATCC 6633 and Streptomyces plumbeus, respectively. Up to now, these potential threonine synthase inhibitors have only been synthesized under enzymatic catalysis. Here we report the chemical stereoselective synthesis of the non-proteinogenic (S,Z)-2-amino-5-phosphonopent-3-enoic acid [(S,Z)-APPA] and its use for the synthesis of Rhizocticin A and Plumbemycin A. In this work, (S,Z)-APPA was synthesized via the Still-Gennari olefination starting from Garner's aldehyde. The Michaelis-Arbuzov reaction was used to form the phosphorus-carbon bond. Oligopeptides were prepared using liquid phase peptide synthesis (LPPS) and were tested against selected bacteria and fungi.
authors.affiliation: Research Center of Cyclotron, University of Liège, Allée du 6 Août 8, Bât B30, B-4000 Sart-Tilman, Liège, Belgium.
authors.forename: Mathias
authors.initials: M
authors.lastname: Gahungu
authors.forename: Anthony
authors.initials: A
authors.lastname: Arguelles-Arias
authors.forename: Patrick
authors.initials: P
authors.lastname: Fickers
authors.forename: Astrid
authors.initials: A
authors.lastname: Zervosen
authors.forename: Bernard
authors.initials: B
authors.lastname: Joris
authors.forename: Christian
authors.initials: C
authors.lastname: Damblon
authors.forename: André
authors.initials: A
authors.lastname: Luxen
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001412:Bacillus subtilis / Q000378:metabolism; D019757:Carbon-Oxygen Lyases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects / Q000201:enzymology; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000201:enzymology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013302:Streptomyces / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D009943:Organophosphorus Compounds; C063847:rhizocticin A; C096637:2-amino-5-phosphono-3-pentenoic acid; C096638:plumbemycin A; D015763:2-Amino-5-phosphonovalerate; D019757:Carbon-Oxygen Lyases; C023160:threonine synthase
keywords: (S,Z)-APPA; Phosphonate antibiotic; Plumbemycin; Rhizocticin; Threonine synthase inhibitors