Reactivity of lysine moieties toward an epoxyhydroxylinoleic acid derivative: aminolysis versus hydrolysis.
Epoxyols are generally accepted as crucial intermediates in lipid oxidation. The reactivity of tert-butyl (9R,10S,11E,13S)-9, 10-epoxy-13-hydroxy-11-octadecenoate (11a,b) toward lysine moieties is investigated, employing N(2)-acetyllysine 4-methylcoumar-7-ylamide (12) as a model for protein-bound lysine. The prefixes R and S denote the relative configuration at the respective stereogenic centers. Independent synthesis and unequivocal structural characterization are reported for 11a,b, its precursors, and tert-butyl (9R,10R,11E, 13S)-10-(¿5-(acetylamino)-6-[(4-methyl-2-oxo-2H-chromen-7-yl)amino ]-6 -oxohexyl¿amino)-9,13-dihydroxy-11-octadecenoate (13a-d). Reactions of 11a,b and 12 in 1-methyl-2-pyrrolidone (MP) and MP/water mixtures at pH 7.4 and 37 degrees C for 56 days show formation of the aminols 13a-d to be favored by an increased water content. The same trend is observed for hydrolytic cleavage of 11a,b to tert-butyl (E)-9,10, 13-trihydroxy-11-octadecenoate (14) and tert-butyl (E)-9,12, 13-trihydroxy-10-octadecenoate (15). Under the given conditions, aminolysis proceeds via an S(N)2 substitution, in contrast with the S(N)1 process for hydrolysis. In the MP/water (8:2) incubation, 15. 8% of 12 has been transformed to 13a-d and 10.5% of 11a,b hydrolyzed to the regioisomers 14 and 15 after 8 weeks, respectively. Aminolysis of alpha,beta-unsaturated epoxides by lysine moieties therefore is expected to be an important mode of interaction between proteins and lipid oxidation products.
Lederer
M O
MO
Institut für Lebensmittelchemie (170), Universität Hohenheim, Garbenstrasse 28, D-70593 Stuttgart, Germany. ledererm@uni-hohenheim.de
Schuler
A
A
Ohmenhäuser
M
M
D006868:Hydrolysis; D006900:Hydroxylation; D008041:Linoleic Acids / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical
D008041:Linoleic Acids; D008239:Lysine