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

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, 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. Copyright © 2008 John Wiley & Sons, Ltd.