Synthesis and Allergenic Potential of a 15-Hydroperoxyabietic Acid-like Model: Trapping of Radical Intermediates

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• 作者：Vincent Mutterer ; Elena Gimé ; nez Arnau ; Ann-Therese Karlberg ; and Jean-Pierre Lepoittevin
• 刊名：Chemical Research in Toxicology
• 出版年：2000
• 出版时间：October 2000
• 年：2000
• 卷：13
• 期：10
• 页码：1028 - 1036
• 全文大小：107K
• 年卷期：v.13,no.10(October 2000)
• ISSN：1520-5010

文摘

To better understand the skin sensitization mechanism of 15-hydroperoxyabietic acid-likecompounds, 2-(1'-hydroperoxy-1'-methylethyl)-4a-methyl-3,4,4a,5,6,7-hexahydronaphthalene 7was synthesized. The allergenic activity of this compound was tested on mice using the locallymph node assay, and further evaluated on guinea pigs using the Freund's complete adjuvanttest. Using these methods, hydroperoxide 7 was found to be a strong sensitizer. Radical-trappingexperiments were carried out on this compound in the presence of the spin-trapping agent,1,1,3,3-tetramethylisoindolin-2-yloxyl 17, using light to induce radicals. The formation of carbon-centered radicals derived from compound 7 by intramolecular cyclization of an oxygen-centeredradical was observed. The reaction of these intermediates with 17 gave various adducts in avery low yield, but a 1/1 mixture of diastereomers 18a and 18b (0.1% yield) was isolated andcharacterized, together with compound 19 (0.03% yield). The results suggest that carbon-centered reactive radicals are formed from allylic hydroperoxides and that this could be thepossible mechanism involved in allergic contact dermatitis to abietic acid.