[2-(3-Halogen-4-hydroxyphenyl)-1,4-napthoquinone derivatives from 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-analogs, potent 5-lipoxygenase inhibitors. 27. 1,4-Naphthoquinones].

A new simple and fast method for the synthesis of halogenated hydroxyphenyl naphthoquinones as potential 5-lipoxygenase (LOX) inhibitors is presented. While the aryl naphthoquinone 1, a potent 5-LOX inhibitor, with AlCl3 is debutylated to 2a and 2b, the oxidized cyclohexadienylidene derivative 3 reacts comparably by concomitant halogenation to 4a and with AlBr3 to 4b, respectively. As products of a side reaction of 6 with TiCl4 and BBr3 the tetracyclic benzo[b]naphthol[2,1-d]furan derivatives 8a and 8b are isolated. Selected compounds are investigated for 5-lipoxygenase inhibiting and antioxidative properties. There is a clear-cut correlation of both qualities in those compounds with a 3-OH function and with two, one or without any tert-butyl group at the phenyl moiety. In contrast the quinone 6 (3-Cl) and the dibenzofuran 8a are powerful 5-LOX inhibitors with only low antioxidative activity.