Trifluoromethanesulfonic acid, an alternative solvent medium for the direct electrophilic fluorination of DOPA: New syntheses of 6-[¹⁸F]fluoro- L-DOPA and 6-[¹⁸F]fluoro-D-DOPA

Previous work from this laboratory has shown that the direct fluorination of 3, 4-dihydroxy-phenyl-L-alanine (L-DOPA) in anhydrous HF (aHF) or BF ₃/HF with F₂ is an efficient method for the synthesis of 6-fluoro-L-DOPA. Since then, ¹⁸F-labeled 6-fluoro-L-DOPA ([ ¹⁸F]6-fluoro-L-DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F₂ toward L-DOPA in CF₃SO₃H is comparable with that in aHF. This new synthetic procedure has led to the production of [¹⁸F] fluoro-L-DOPA and [¹⁸F]fluoro-L-DOPA isomers in 17 ± 2% radiochemical yields (decay corrected with respect to [¹⁸F]F ₂). The 2- and 6-FDOPA isomers were separated by HPLC and subsequently characterized by ¹⁹F NMR spectroscopy. The corresponding [¹⁸F]-FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF.