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 synthes ised with defined stereochemistry. Densely functionalised hydroxylamine con taining amino acids were prepared by the addition of a glycine anion equiva lent to sugar-derived cyclic nitrones. One of four stereoisomeric dipeptide s incorporating these novel amino acids was found to be a potent and select ive inhibitor of bacterial tyrosyl tRNA synthetase, suggesting analogous st ereochemistry of the natural product. (C) 2000 Elsevier Science Ltd. All ri ghts reserved.