Synthesis, Discovery, and Quantitation of Dihomo-Isofurans: Biomarkers for In Vivo Adrenic Acid Peroxidation

• Published in: Angewandte Chemie International Edition 2014-06, Vol.53 (24), p.6249-6252
• Main Authors: de La Torre, Aurélien, Lee, Yiu Yiu, Oger, Camille, Sangild, Per Torp, Durand, Thierry, Lee, Jetty Chung-Yung, Galano, Jean-Marie
• Format: Article
• Language: English
• Subjects: Biomarkers; Brain; Chemical Sciences; Fatty acids; Fatty Acids, Unsaturated - chemical synthesis; Fatty Acids, Unsaturated - chemistry; Furans - chemical synthesis; Furans - chemistry; In vivo testing; In vivo tests; Lipid Peroxidation; Lipids; mass spectrometry; Metabolites; Organic chemistry; oxidation; Strategy; Synthesis; total synthesis
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201402440

The growing importance of lipidomics, and the interest of non‐enzymatic metabolites of polyunsaturated fatty acids (PUFAs) prompted us to initiate the synthesis of novel dihomo‐IsoF compounds. Such metabolites of adrenic acid, the main PUFA in white matter, were synthesized using a divergent approach based on an orthoester cyclization. LC‐MS/MS investigation on pig brains showed the potential of this novel biomarker for the first time, as a powerful new tool for brain lipid peroxidation assessment. White matter matters: The enantioselective synthesis of dihomo‐Isofurans (dihomo‐IsoFs), metabolites from in vivo peroxidation of adrenic acid (found in white matter of the brain), is described and employs a C2‐symmetric precursor in a divergent strategy. Mass‐spectrometry analysis accurately validated its presence in pig brain, and quantitation analysis showed, for the first time, the importance of such a novel biomarker in assessing lipid peroxidation.