Enantioselective synthesis of [18F]fluoro-L-aromatic amino acids, such as 6-[18F]fluoro-L-dopa and 2-[18F]fluoro-L-tyrosine

Amino acids labelled with the short-lived positron emitter 18F are useful compounds for studying in vivo human brain metabolism by Positron Emission Tomography. Although amino acids are involved in several metabolisms, [18F]fluoro-L-aromatic amino acids, such as 6-[18F]fluoro-L-dopa and 2-[18F]fluoro-L-tyrosine, have been mainly synthesized and used for probing the dopaminergic system and protein synthesis. The need for reliable production of these enantiomerically pure radiopharmaceuticals has led during the last past years to reports of various electrophilic ([18F]F2, CH3COO18F) and nucleophilic (18F-) syntheses for these radiopharmaceuticals. For this purpose, the chemist can perform the syntheses through different pathways: (I) from an optically active synthon and avoid racemisation, (II) to sythesize a racemate and resolve it, (III) to induce the chiral center in an enantioselective or preferable enantiospecific synthesis. These various synthetic aspects of [18F]fluorination are discussed