| Abstract: | The thioridazine metabolites 7-hydroxythioridazine (2a) and 7-hydroxysulforidazine (2b) were synthesized. Commercial 4-chloro-3-nitrophenylmethylsulfone was converted to the corresponding 4-thiol through an intermediate xanthate ester. Subsequent zinc metal reduction provided the 3-amino thiolate. This salt was condensed with chloroquinone to yield 7-hydroxy-2-methylsulfonylphenothiazine which was then protected as the isopropyl ether. N-Alkylation with 2-(2-chloroethyl)-1-methylpiperidine using sodium hydroxide, then ether cleavage, afforded 2b . The N-alkylation followed by reduction with diisobutylaluminum hydride and deblocking yielded 2a . These reference standards will assist in an exploration of the potential role of meta-bolically formed 2a and 2b in the neuroleptic response to thioridazine. |
