RESUMO
In this study, the synthesis of N-alkyl-2-halophenazin-1-ones has been established. Six N-alkyl-2-halophenazin-1-ones, including WS-9659 B and marinocyanins A and B, were synthesized by the direct oxidative condensation of 4-halo-1,2,3-benzenetriol with the corresponding N-alkylbenzene-1,2-diamines. One of the most significant features of the present method is that it can be successfully applied to the synthesis of N-alkyl-2-chlorophenazin-1-ones. The traditional chlorination of N-alkyl-phenazin-1-ones with N-chlorosuccinimide selectively occurs at the 4-position to afford the undesired N-alkyl-4-chlorophenazin-1-ones. Our synthetic route successfully circumvents this problem, culminating in the first chemical synthesis of WS-9659 B. The cytotoxicity of six N-alkyl-2-halophenazin-1-ones and three N-alkylphenazin-1-ones against human promyelocytic leukemia HL-60, human lung cancer A549, and normal MRC-5 cells was evaluated. Among the compounds tested in this study, 2-chloropyocyanin possesses significant selectivity toward A549 cells. The cytotoxic evaluation provides structural insights into the potency and selectivity of these compounds for cancer cells.
RESUMO
Total syntheses of pyocyanin, lavanducyanin, and marinocyanins A and B have been accomplished. The N-substituted phenazin-1-one skeleton, a common framework of these natural products, was constructed through the oxidative condensation of pyrogallol with N-substituted benzene-1,2-diamine under an oxygen atmosphere in a single step. Regioselective bromination with N-bromosuccinimide at the C-2 position of N-alkylated phenazin-1-ones afforded brominated natural products.
