Abstract
Alpha-linolenic acid (ALA), an essential omega-3 polyunsaturated fatty acid found in plants, exertsneuroprotection and anti-inflammatory effects in chronic and acute CNS disease models. However, theunderlying mechanisms are not yet understood. Since ALA is not incorporated into the brain, theobserved health benefits may result from some of its metabolites. The putative formation of dihydroxylatedALA derivatives (called linotrins) was recently shown in vitro in the presence of lipoxygenases.However, the in vitro biosynthesis of linotrins was neither stereoselective nor quantitatively efficient forstudying their physiological roles as enantiomeric pure forms. Herein, we report the first stereocontrolledsynthesis that features regio- and stereoselective hydrometalations of alkynes for assemblingthe sensitive E,Z,E-conjugated trienes, as well as LC-MS investigations that provide evidence oflinotrins occurrence in plants. Moreover, strong anti-inflammatory effects on microglia highlight thepotential physiological importance of linotrins and open new perspectives in search of CNS therapeutics.