Inhibitors of bacterial tyrosyl tRNA synthetase: synthesis of four stereoisomeric analogues of the natural product SB-219383.
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.
Berge
J M
JM
SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
Copley
R C
RC
Eggleston
D S
DS
Hamprecht
D W
DW
Jarvest
R L
RL
Mensah
L M
LM
O'Hanlon
P J
PJ
Pope
A J
AJ
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*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D005663:Furans; C410784:SB 219383; D014448:Tyrosine-tRNA Ligase