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-F 3t-IsoP and 10-F4t-NeuroP and its deuterated derivative from acetylenic intermediateA (see scheme). Such compounds represent potential biomarkers of neuronal oxidative stress. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim