Inhibitors of bacterial tyrosyl tRNA synthetase: synthesis of four stereoisomeric analogues of the natural product SB-219383

• Published in: Bioorganic & medicinal chemistry letters Vol. 10; no. 16; pp. 1811 - 1814
• Main Authors: Berge, John M, Copley, Royston C.B, Eggleston, Drake S, Hamprecht, Dieter W, Jarvest, Richard L, Mensah, Lucy M, O'Hanlon, Peter J, Pope, Andrew J
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 21-08-2000; Elsevier
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial Physiological Phenomena; Biological and medical sciences; Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis; Bridged Bicyclo Compounds, Heterocyclic - chemistry; Chemistry, Organic; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Furans - chemical synthesis; Furans - chemistry; Magnetic Resonance Spectroscopy; Medical sciences; Molecular Structure; Organic Chemistry Phenomena; Pharmacology. Drug treatments; Stereoisomerism; Tyrosine-tRNA Ligase - antagonists & inhibitors; Stereoisomer; Peptides; Enzyme; Enzyme inhibitor; Tyrosine-tRNA ligase; In vitro; Structure activity relation; Ligases; Piperidine derivatives; Dipeptides; Bacteria; Micrococcales; Micrococcaceae; Antibacterial agent; Chemical synthesis; Carbon-oxygen ligases; Triol; Organic hydroxylamine; Staphylococcus aureus
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(00)00348-6

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.