6937-96-8Relevant articles and documents
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Koller,Kandler
, p. 234 (1930)
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Chemical reactivity and skin sensitization potential for benzaldehydes: Can Schiff base formation explain everything?
Natsch, Andreas,Gfeller, Hans,Haupt, Tina,Brunner, Gerhard
, p. 2203 - 2215 (2013/01/15)
Skin sensitizers chemically modify skin proteins rendering them immunogenic. Sensitizing chemicals have been divided into applicability domains according to their suspected reaction mechanism. The widely accepted Schiff base applicability domain covers aldehydes and ketones, and detailed structure-activity-modeling for this chemical group was presented. While Schiff base formation is the obvious reaction pathway for these chemicals, the in silico work was followed up by limited experimental work. It remains unclear whether hydrolytically labile Schiff bases can form sufficiently stable epitopes to trigger an immune response in the living organism with an excess of water being present. Here, we performed experimental studies on benzaldehydes of highly differing skin sensitization potential. Schiff base formation toward butylamine was evaluated in acetonitrile, and a detailed SAR study is presented. o-Hydroxybenzaldehydes such as salicylaldehyde and the oakmoss allergens atranol and chloratranol have a high propensity to form Schiff bases. The reactivity is highly reduced in p-hydroxy benzaldehydes such as the nonsensitizing vanillin with an intermediate reactivity for p-alkyl and p-methoxy-benzaldehydes. The work was followed up under more physiological conditions in the peptide reactivity assay with a lysine-containing heptapeptide. Under these conditions, Schiff base formation was only observable for the strong sensitizers atranol and chloratranol and for salicylaldehyde. Trapping experiments with NaBH3CN showed that Schiff base formation occurred under these conditions also for some less sensitizing aldehydes, but the reaction is not favored in the absence of in situ reduction. Surprisingly, the Schiff bases of some weaker sensitizers apparently may react further to form stable peptide adducts. These were identified as the amides between the lysine residues and the corresponding acids. Adduct formation was paralleled by oxidative deamination of the parent peptide at the lysine residue to form the peptide aldehyde. Our results explain the high sensitization potential of the oakmoss allergens by stable Schiff base formation and at the same time indicate a novel pathway for stable peptide-adduct formation and peptide modifications by aldehydes. The results thus may lead to a better understanding of the Schiff base applicability domain.
Stereoselective synthesis of 4-dehydroxydiversonol employing enantioselective palladium-catalysed domino reactions
Tietze, Lutz F.,Spiegl, Dirk A.,Stecker, Florian,Major, Julia,Raith, Christian,Grosse, Christian
experimental part, p. 8956 - 8963 (2009/10/10)
The stereoselective synthesis of 4-dehydroxydiversonol (4) employing enantioselective palladium-catalysed domino processes such as the domino Wacker-Heck and the domino Wacker-carbonylation reaction for the formation of the central chroman moiety is described. Thus, reaction of 8 with palladium(II) trifluoroacetate [Pd(OTFA)2] in the presence of carbon monoxide, methanol and the 2,2′-bis(oxazolin-2-yl)-1,1'-binaphthyl (BOXAX) ligand 17 led to 19 in 80% yield and 96% ee. Similarly, the chroman 7 was prepared using 8 and methyl acrylate (9) as starting material. Hydrogenation of the double bond, oxidation of the benzylic methylene group and intramolecular acylation of chromanone 6 provided the tetrahydroxanthenone core 5, from which the synthesis of 4 was completed. The relative configuration of 4 could be established by crystal structure analysis.
