Enantioselective Synthesis of 7(S)‑Hydroxydocosahexaenoic Acid, a Possible Endogenous Ligand for PPARα

We report the first total synthesis of the polyunsaturated fatty acid 7-hydroxydocosahexaenoic acid (7-HDHA) in racemic form and the enantioselective synthesis of 7-(S)-HDHA. Both syntheses follow a convergent approach that unites the C1–C9 and C10–C22 fragments using Sonogashira coupling and Boland reduction as key steps. These syntheses enabled the unambiguous characterization of this natural product for the first time and helped establish 7­(S)-HDHA as a possible endogenous ligand for peroxisome proliferator-activated receptor alpha.