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

The aim of this work was to synthesize 13C 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 13C precursor [1,2‐13C2]‐4‐[(tetrahydro‐2H‐pyran‐2‐yl)oxy]‐2(E)‐nonenal. [1,2‐13C2]‐HNE was obtained by acid deprotection. All the intermediary and final compounds were fully characterized by IR, HRMS, 1H and 13C NMR. It is the first synthesis of HNE which enables the incorporation of two 13C labels at determined positions. Copyright © 2008 John Wiley & Sons, Ltd. The aim of this work was to synthesize 13C 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 precursor of HNE. The scheme was then used to produce the 13C precursor [1,2‐13C2]‐4‐[(tetrahydro‐2H‐pyran‐2‐yl)oxy]‐2(E)‐nonenal for [1,2‐13C2]‐HNE preparation. Copyright © 2008 John Wiley & Sons, Ltd.