A short synthesis of [14C]-labelled levamisole and its major metabolite

Levamisole (1) is the levo isomer of tetramisole. It is a broad spectrum anthelmintic which is used extensively as a veterinary drug for food producing animals. Metabolism and environmental studies necessitated the synthesis of C-14-labelled levamisole (6) and of its major metabolite (12). C-14-Tetramisole was obtained in two steps from C-14-thiourea. Resolution via salt formation and crystallization afforded C-14-levamisole and 14 C-dexamisole. Racemisation followed again by resolution made it possible to improve the over-all radiochemical yield of C-14-levamisole to 51.0%. The compound had a specific activity of 73.6MBq/mmol., a HPLC purity of 99.8% and an enantiomeric excess of 99.4%. The C-14-labelled metabolite of levamisole (II) was obtained from C-14-potassium cyanate in 4 consecutive steps. Resolution via chiral HPLC afforded the desired compound in a 16.2% overall radiochemical yield. It had a specific activity of 895 MBq/mmol, a HPLC purity of 98.7% and an enantiomeric excess of 100%. Copyright (C) 2002 John Wiley Sons, Ltd.