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Facile Syntheses of the Three Major Metabolites of Thioridazine
Author(s) -
Morrow Ryan J.,
Millership Jeff S.,
Collier Paul S.
Publication year - 2005
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200590089
Subject(s) - chemistry , sulfoxide , thioridazine , moiety , metabolite , yield (engineering) , column chromatography , sulfide , organic chemistry , chromatography , combinatorial chemistry , biochemistry , pharmacology , medicine , materials science , chlorpromazine , metallurgy
Abstract Efficient, mild syntheses of the three major metabolites 2 – 4 of the important antipsychotic drug thioridazine ( 1 ) have been developed. The cardiotoxic metabolite 2 with a ring sulfoxide moiety was prepared in 96% yield by oxidation of 1 with NaIO 4 under acidic conditions. Four different procedures were elaborated for the selective side‐chain sulfide oxidation of 1 to mesoridazine ( 3 ), giving rise to yields of up to 91%. Finally, sulforidazine ( 4 ) was synthesised via oxidation of the sulfoxide 3 in the presence of either KMnO 4 or t ‐BuOOH under basic conditions. Except for the oxidation with t ‐BuOOH, all reactions took place under mild conditions within a few minutes, were nicely reproducible, and afforded medium‐to‐high yields of the desired products, which could be readily purified by column chromatography.