Synthesis of Allylic Hydroperoxides and EPR Spin-Trapping Studies on the Formation of Radicals in Iron Systems as Potential Initiators of the Sensitizing Pathway

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• 作者：Dany Kao ; Alain Chaintreau ; Jean-Pierre Lepoittevin ; Elena Gime虂nez-Arnau
• 刊名：Journal of Organic Chemistry
• 出版年：2011
• 出版时间：August 5, 2011
• 年：2011
• 卷：76
• 期：15
• 页码：6188-6200
• 全文大小：1138K
• 年卷期：v.76,no.15(August 5, 2011)
• ISSN：1520-6904

文摘

Many terpenes used as fragrance compounds autoxidize when exposed to air, forming allylic hydroperoxides that have the potential to be skin contact allergens. To trigger the immunotoxicity process that characterizes contact allergy, these hydroperoxides are supposed to bind covalently to proteins in the skin via radical pathways. We investigated the formation of reactive radical intermediates from 7-hydroperoxy-3,7-dimethylocta-1,5-dien-3-ol and 2-hydroperoxylimonene, responsible for the sensitizing potential acquired by autoxidized linalool and limonene. Both compounds were synthesized through new short and reproducible synthetic pathways. The hydroperoxide decomposition catalyzed by Fe(II)/Fe(III) redox systems, playing a key role in degradating peroxides in vivo, was examined by spin-trapping-EPR spectroscopy. Alkoxyl and carbon-centered free radicals derived from the hydroperoxides were successfully trapped by the spin-trap 5,5-dimethyl-1-pyrroline N-oxide, whereas peroxyl radicals were characterized by spin-trapping studies with 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide. Using liquid chromatography combined with mass spectrometry, we demonstrated the formation of adducts, via radical mechanisms induced by Fe(II)/Fe(III), between the hydroperoxides and N-acetylhistidine methyl ester, a model amino acid that is prone to radical reactions. Free radicals derived from these hydroperoxides can thus induce amino acid chemical modifications via radical mechanisms. The study of these mechanisms will help to understand the sensitizing potential of hydroperoxides.