Arnold R. Martin

Induced formation of phenylalanine ammonia lyase and pisatin by chlorpromazine and other phenothiazine derivatives

Abstract Chlorpromazine and 16 other phenothiazine derivatives induced up to 11-fold increases in phenylalanine ammonia lyase activity and the de novo synthesis of up to 200 μg pisatin per g of pea pod tissue. The induction of phenylalanine ammonia lyase was dependent on new RNA and protein synthesis and was accompanied by increased synthesis of an array of cellular proteins.

1,2-Didehydrophenothiazines: preparation of 1-alkyl and 1-aryl-substituted phenothiazines by lithium-directed alkylation

A general route to 1-alkyl substituted phenothiazines is described. Reactions of 2-chlorophenothiazine with an excess of methyl-, n-butyl-, s-butyl, t-butyl-or phenyl-lithiums give the corresponding 1-substituted phenothiazines via 10-lithio-1,2-dehydrophenothiazine. Attempts to trap the presumed 1,10-dilithio intermediate failed. The reaction of 1-chlorophenothiazine with s-butyl-lithium results in preferential metallation of the 9-position. 2-Chlorophenothiazine reacts with nitrogen nucleophiles (lithium dialkylamides) to give 2-substituted products.