61203-67-6Relevant articles and documents
Mechanistic Insights on Skin Sensitization to Linalool Hydroperoxides: EPR Evidence on Radical Intermediates Formation in Reconstructed Human Epidermis and 13C NMR Reactivity Studies with Thiol Residues
Kuresepi, Salen,Vileno, Bertrand,Lepoittevin, Jean-Pierre,Giménez-Arnau, Elena
, p. 1922 - 1932 (2020)
Linalool is one of the most commonly used fragrance terpenes in consumer products. While pure linalool is considered as non-allergenic because it has a very low skin sensitization potential, its autoxidation on air leads to allylic hydroperoxides that have been shown to be major skin sensitizers. These hydroperoxides have the potential to form antigens via radical mechanisms. In order to obtain in-depth insights of such reactivity, we first investigated the formation of free radicals derived from linalool hydroperoxides in situ in a model of human reconstructed epidermis by electron paramagnetic resonance combined with spin trapping. The formation of carbon- and oxygen-centered radical species derived from the hydroperoxides was especially evidenced in an epidermis model, mimicking human skin and thus closer to what may happen in vivo. To further investigate these results, we synthesized linalool hydroperoxides containing a 13C-substitution at positions precursor of carbon radicals to elucidate if one of these positions could react with cysteine, its thiol chemical function being one of the most labile groups prone to react through radical mechanisms. Reactions were followed by mono- and bidimensional 13C NMR. We validated that carbon radicals derived from allylic hydrogen abstraction by the initially formed alkoxyl radical and/or from its β-scission can alter directly the lateral chain of cysteine forming adducts via radical processes. Such results provide an original vision on the mechanisms likely involved in the reaction with thiol groups that might be present in the skin environment. Consequently, the present findings are a step ahead toward the understanding of protein binding processes to allergenic allylic hydroperoxides of linalool through the involvement of free radical species and thus of their sensitizing potential.
Simple and efficient preparation of [10,20-13C2]- and [10-CH3,13-13C2]-10-methylretinal: Introduction of substituents at the 2-position of 2,3-unsaturated nitriles
Verdegem,Monnee,Lugtenburg
, p. 1269 - 1282 (2007/10/03)
In this paper, we present the synthesis of [10,20-13C2]-10-methylretinal and [10-CH3,13-13C2]-10-methylretinal, two doubly 13C-labeled chemically modified retinals that have been recently used to study the structural and functional details behind the photocascade of bovine rhodopsin (Verdegem et al. Biochemistry 1999, 38, 11316; de Lange et al. Biochemistry 1998, 37, 1411). To obtain both doubly 13C-labeled compounds, we developed a novel synthetic method to directly and regiospecifically introduce a methyl substituent on the 2-position of 3-methyl-5-(2′,6′,6′-trimethyl-1′ -cyclohexen-1′-yl)-2,4-pentadienenitrile. Encouraged by these results, we investigated the scope of this novel reaction by developing a general method for the introduction of a variety of substituents to the 2-position of 3-methyl-2,3-unsaturated nitriles, paving the way for simple and efficient synthesis of a wide variety of 10-, 14-, and 10,14-substituted chemically modified retinals, and other biologically important compounds.
THE SYNTHESIS OF C-13 LABELED VITAMIN E, all-rac-α-TOCOPHEROL
Urano, Shiro,Otani, Ikuko,Matsuo, Mitsuyoshi
, p. 2793 - 2796 (2007/10/02)
Vitamin E with a 13C-labeled isoprenoid side chain, all-rac-α-tocopherol (1), was synthesized using 6-methoxymethoxy-2,5,7,8-tetramethyl-2-chroman (6) as a key intermediate and ethyl bromoacetate as a 13C source.The overall yield of 1 based on ethyl bromoacetate was 19.2percent.
