Interactions of allergenic hydroperoxides with proteins: a radical mechanism?

1-(1-Hydroperoxy-1-methylethyl)cyclohexene was synthesized as a model compound for the study of the interaction of 15-hydroperoxyabietic acid-like terpenes with proteins. Two related epoxides, 1-(1-hydroxy-1-methylethyl)-2-oxabicyclo[4.1.0]heptane and 2,2-dimethyl-1-oxaspiro-[2.5]octan-4-ol, were also prepared as reference materials. Treatment of the hydroperoxide with FeCl3 and N alpha-Ac-Cys-OMe led to the formation of the corresponding alcohol and of both epoxides. The allergenic activity of these compounds was tested in guinea pigs using the Freund's complete adjuvant test. The hydroperoxide was found to be a strong sensitizer while both epoxides were found to be inactive at the same doses. The generation of highly-reactive radicals in the epidermis could lead to the formation of antigenic structures, the first step of the allergic contact dermatitis mechanism.