Oxygenated Metabolites of n-3 Polyunsaturated Fatty Acids as Potential Oxidative Stress Biomarkers: Total Synthesis of 8-F3t-IsoP, 10-F4t-NeuroP and [D4]-10-F4t-NeuroP

A wide variety of metabolic products of polyunsaturated fatty acids is of paramount importance for improving our medical knowledge in the field of oxidized lipids. Two novel metabolites of n‐3 polyunsaturated fatty acids, 8‐F3t‐IsoP and 10‐F4t‐NeuroP as well as a deuterated derivative thereof were synthesized based on an acetylenic intermediate. An original approach achieved lateral chain insertion of 8‐F3t‐IsoP by a ring‐closing alkyne metathesis/semi‐reduction strategy together with a temporary tether. Three for the price of one! Two strategies, Caruso coupling or ring‐closing alkyne metathesis (RCAM), enabled the synthesis of 8‐F3t‐IsoP and 10‐F4t‐NeuroP and its deuterated derivative from acetylenic intermediate A (see scheme). Such compounds represent potential biomarkers of neuronal oxidative stress.