Synthesis of the lipid peroxidation product 4-hydroxy-2(E)-nonenal with ~(13)C stable isotope incorporation

摘要

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)oxy]-2(E)-nonenal. This compound is a precursor of HNE. The scheme was then used to produce the ~(13)C precursor [1,2-~(13)C_2]-4-[(tetrahydro-2H-pyran-2-yl)oxy]-2(E)-nonenal. [1,2-~(13)C_2]-HNE was obtained by acid deprotection. All the intermediary and final compounds were fully characterized by IR, HRMS, ~1H and ~(13)C NMR. It is the first synthesis of HNE which enables the incorporation of two ~(13)C labels at determined positions.