title: Inhibitors of bacterial tyrosyl tRNA synthetase: synthesis of four stereoisomeric analogues of the natural product SB-219383.
abstract: Synthetic analogues of the microbial metabolite SB-219383 have been synthesised with defined stereochemistry. Densely functionalised hydroxylamine containing amino acids were prepared by the addition of a glycine anion equivalent to sugar-derived cyclic nitrones. One of four stereoisomeric dipeptides incorporating these novel amino acids was found to be a potent and selective inhibitor of bacterial tyrosyl tRNA synthetase, suggesting analogous stereochemistry of the natural product.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Berge
authors.forename: R C
authors.initials: RC
authors.lastname: Copley
authors.forename: D S
authors.initials: DS
authors.lastname: Eggleston
authors.forename: D W
authors.initials: DW
authors.lastname: Hamprecht
authors.forename: R L
authors.initials: RL
authors.lastname: Jarvest
authors.forename: L M
authors.initials: LM
authors.lastname: Mensah
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Hanlon
authors.forename: A J
authors.initials: AJ
authors.lastname: Pope
mesh_terms: D018407:Bacterial Physiological Phenomena; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D002625:Chemistry, Organic; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D055601:Organic Chemistry Phenomena; D013237:Stereoisomerism; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D005663:Furans; C410784:SB 219383; D014448:Tyrosine-tRNA Ligase