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

Abstract 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 F 2 is an efficient method for the synthesis of 6‐fluoro‐ L ‐DOPA. Since then, 18 F‐labeled 6‐fluoro‐ L ‐DOPA ([ 18 F]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 F 2 toward L ‐DOPA in CF 3 SO 3 H is comparable with that in aHF. This new synthetic procedure has led to the production of [ 18 F]fluoro‐ L ‐DOPA and [ 18 F]fluoro‐D‐DOPA isomers in 17±2% radiochemical yields (decay corrected with respect to [ 18 F]F 2 ). The 2‐ and 6‐FDOPA isomers were separated by HPLC and subsequently characterized by 19 F NMR spectroscopy. The corresponding [ 18 F]‐FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF. Copyright © 2007 John Wiley & Sons, Ltd.