Synthesis and biological evaluation of non-natural analogues of nitro-fatty acids

Abstract

Nitroalkene fatty acids, so-called nitrated or nitro-fatty acids (NO2-FAs or NFAs), and the corresponding nitrated lipids are naturally occurring electrophiles. They are produced by the nitration of unsaturated fatty acids with nitric oxide-derived radicals, especially during inflammation processes. Nitro-fatty acids have emerged as a novel class of signaling molecules with strong anti-inflammatory and also anti-tumorigenic effects. As potent electrophiles, NFAs mainly act by post-translational modification of proteins through the addition of nucleophilic amino acid side chains to reactive nitroolefin. Within the framework of this doctoral thesis, it was possible to synthesize non-natural analogues of nitro fatty acids containing different electron-withdrawing groups incorporated into the fatty acid chain in proximal (part I) and distal (part II) position to the terminal carboxyl group via alkyne-based approach (Scheme). Using this novel approach, we could synthesize a library of around 30 novel structurally diverse electrophilic fatty acids