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

J M Berge; R C Copley; D S Eggleston; D W Hamprecht; R L Jarvest; L M Mensah; P J O'Hanlon; A J Pope

doi:10.1016/s0960-894x(00)00348-6

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

Bioorg Med Chem Lett. 2000 Aug 21;10(16):1811-4. doi: 10.1016/s0960-894x(00)00348-6.

Authors

J M Berge¹, R C Copley, D S Eggleston, D W Hamprecht, R L Jarvest, L M Mensah, P J O'Hanlon, A J Pope

Affiliation

¹ SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.

PMID: 10969974
DOI: 10.1016/s0960-894x(00)00348-6

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.

MeSH terms

Bacterial Physiological Phenomena
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
Molecular Structure
Organic Chemistry Phenomena
Stereoisomerism
Tyrosine-tRNA Ligase / antagonists & inhibitors*

Substances

Bridged Bicyclo Compounds, Heterocyclic
Enzyme Inhibitors
Furans
SB 219383
Tyrosine-tRNA Ligase