2-(3-halogen-4-hydroxyphenyl)-1,4-naphthoquinones from their 2-(3,5-di-tert-butyl-4-hydroxyphenyl) congeners, potent 5-lipoxygenase inhibitors - 1,4-naphthoquinones, XXVII

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 d ebutylated to 2a and 2b, the oxidized cyclohexadienylidene derivative 3 rea cts comparably by concomitant halogenation to 4a and with AlBr3 to 4b, resp ectively. As products of a side reaction of 6 with TiCl4 and BBr3 the tetra cyclic benzo[b]naphthol[2, 1-d]furan derivatives 8a and 8b are isolated. Se lected compounds are investigated for 5-lipoxygenase inhibiting and antioxi dative properties. There is a clear-cut correlation of both qualities in th ose compounds with a 3-OH function and with two, one or without any tert-bu tyl group at the phenyl moiety. In contrast the quinone 6 (3-Cl) and the di benzofuran 8a are powerful 5-LOX inhibitors with only low antioxidative act ivity.