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Synthesis of 3 H‐labelled levamisole
Author(s) -
Thijssen J. J. A.,
Knaeps A. A.,
Verluyten W. W. M.,
Heykants J. J. P.,
Janssen C. C. M.
Publication year - 1987
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580240708
Subject(s) - chemistry , thiazole , high performance liquid chromatography , hydrolysis , yield (engineering) , levamisole , halogenation , amination , medicinal chemistry , anthelmintic , organic chemistry , catalysis , medicine , ecology , materials science , metallurgy , biology
Levamisole, the levo isomer of tetramisole, is a potent anthelmintic also showing immunotropic properties. Renewed interest in the latter domain necessitated the synthesis of specifically 3 H‐labelled levamisole of high specific activity. Racemic 1‐(2‐bromophenyl)‐1,2‐ethane diamine dihydrochloride ( V ) was obtained via bromination of 1‐(2‐bromophenyl)ethanone ( I ), followed by reaction with 2,5‐pyrrolidinedione, Leuckart amination and hydrolysis. The racemate was then resolved by successive salt formation with (S)‐(‐) and (R)‐(+) tartaric acid. The liberated (S)‐(+)‐base of VI was dehalogerated with approximately 30 Ci of tritium gas and immediately ring‐closed with carbon disulfide to VIII . The HPLC‐purified material was finally cyclized with 1,2‐dibromo ethane to (S)‐(‐)‐2,3,5,6‐tetrahydro‐6‐[2‐T]phenyl‐imidazo‐(2,1‐b)‐thiazole IX and the isomerically ringclosed (S)‐2,3,5,6‐tetrahydro‐5‐[2‐T] phenyl‐imidazo‐(2,1‐b)‐thiazole X , of which levamisole IX was isolated via HPLC. The radiochemical yield over the cyclization steps was 28.2 %, the specific activity was 10.82 Ci/mmol, and the product was 99.9 % HPLC pure.