Skin Sensitization to Linalyl Hydroperoxide: Support for Radical Intermediates

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• 作者：Michael Bezard ; Ann-Therese Karlberg ; Johan Montelius ; and Jean-Pierre Lepoittevin
• 刊名：Chemical Research in Toxicology
• 出版年：1997
• 出版时间：September 1997
• 年：1997
• 卷：10
• 期：9
• 页码：987 - 993
• 全文大小：188K
• 年卷期：v.10,no.9(September 1997)
• ISSN：1520-5010

文摘

In order to better understand the skin sensitizationmechanism of allylic hydroperoxides,linalyl hydroperoxide (1) and several of its potentialrearrangement products-epoxylinalool(2), epoxynerol (3), epoxygeraniol(4), and furan (5) and pyran (6)derivatives-were synthesized.The sensitizing properties of these molecules have been screenedon mice using the local lymphnode assay (LLNA) and further evaluated on guinea pigs using theFreund's complete adjuvanttest (FCAT). Linalyl hydroperoxide (1) and linalylepoxide (2) were found to be sensitizers,while the other compounds were classified as mild sensitizers ornonsensitizers. In the guineapigs, no cross-reactions were observed between skin sensitizers1 and 2. Radical-trappingexperiments were carried out on linalyl hydroperoxide (1)using TTBP as trapping agent andFe³⁺-TPP as radical inducer. The major reactiontaking place is the formation of a furan ringby intramolecular reaction of the oxygen-centered radical with theisoprenyl double bond withthe formation of a tertiary radical. Reaction of this intermediatewith radicals derived fromTTBP gave compounds 10a,b in 25% yield. Thesecond important reaction, accounting for14%, is taking place on the allylic double bond with the formation ofa less stable primaryradical which is not trapped by a TTBP-derived radical but by a hydroxyradical to give amixture of epoxides 3 and 4. These resultsare in favor of the formation of a carbon-centeredreactive radical as intermediate in the skin sensitization to linalylhydroperoxide.