2-ANTHRACENONYL ACETIC-ACIDS AS 5-LIPOXYGENASE INHIBITORS

The synthesis of 2-substituted anthracenonyl acetic (2-AA) derivatives is described. The key step is the Marschalk reaction of 1-hydroxy-8-m ethoxy-anthracenedione with glycolic acid. After protection of the res ulting 2-anthracenonyl acetic acid derivative, the 2-monalkylated deri vatives are selectively obtained by direct alkylation. The methodology proves quite general and allows for the introduction of various subst ituents onto the 2-position of the carboxylic side chain. Reduction of the anthracenediones proceeds with carboxylic side chain. Reduction o f the anthracenediones proceeds with concomitant protecting group remo val and provides final 2-AA products in good yields. The results of in itial biological studies demonstrate enhanced 5-lipoxygenase inhibitio n compared to anthralin.