The enzymatic synthesis of isotopically labelled penicillin Ns with isopenicillin N synthase

The preparation of isotopically labelled penicilllin Ns using a chemico-enz ymatic approach is described. This route involves the chemical synthesis of variously labelled (D) under bar,(L) under bar,(D) under bar,-aminoadipoyl -cysteinyl-valine tripeptides via well established facile protocols and con cludes with the conversion of these tripeptides directly into penicillin Ns by the action of recombinant isopenicillin N synthase. Milligram quantitie s of isotopically labelled penicillin Ns, which would otherwise represent v ery challenging and expensive synthetic targets, are readily accessible fro m this route.