Synthesis of the lipid peroxidation product 4-hydroxy-2(E)-nonenal with (13)C stable isotope incorporation
Résumé
The aim of this work was to synthesize (13)C internal standards for the quantification of 4-hydroxy-2(E)-nonenal(HNE), a lipid peroxidation product, and of the etheno-adducts possibly formed by HNE damage to DNA nucleobases. We designed an eight-step synthesis starting from ethyl 2-bromoacetate and giving access to 4-[(tetrahydro-2H-pyran-2-yl)oxrl-2(E)nonenal. This compound is a precursor of HNE. The scheme was then used to produce the 13C precursor [1,2- (13)C(2)]-4-[(tetrahydro-2H-pyran-2-yl)oxyl-2(E)-nonenal. [1,2- (13)C(2)]-HNE was obtained by acid cleprotection. All the intermediary and final compounds were fully characterized by IR, HRMS, (1)H and (13)C NMR. it is the first synthesis of HNE which enables the incorporation Of two (13)C labels at determined positions.