Synthesis and allergenic potential of a 15-hydroperoxyabietic acid-like model: Trapping of radical intermediates

To better understand the skin sensitization mechanism of 15-hydroperoxyabie tic acid-like compounds, 2-(1'-hydroperoxy-1'-methylethyl)-4a-methyl-3,4,4a ,5,6,7-hexahydronaphthalene 7 was synthesized. The allergenic activity of t his compound was tested on mice using the local lymph node assay, and furth er evaluated on guinea pigs using the Freund's complete adjuvant test. Usin g these methods, hydroperoxide 7 was found to be a strong sensitizer. Radic al-trapping experiments were carried out on this compound in the presence o f the spin-trapping agent, 1,1,3,3-tetramethylisoindolin-2-yloxyl 17, using light to induce radicals. The formation of carbon-centered radicals derive d from compound 7 by intramolecular cyclization of an oxygen-centered radic al was observed. The reaction of these intermediates with 17 gave various a dducts in a very low yield, but a 1/1 mixture of diastereomers 18a and 18b (0.1% yield) was isolated and characterized, together with compound 19 (0.0 3% yield). The results suggest that carbon-centered reactive radicals are f ormed from allylic hydroperoxides and that this could be the possible mecha nism involved in allergic contact dermatitis to abietic acid.