FLUORINE FOR HYDROXY SUBSTITUTION IN BIOGENIC-AMINES - ASYMMETRIC-SYNTHESIS AND BIOLOGICAL EVALUATION OF FLUORINE-18-LABELED BETA-FLUOROPHENYLALKYLAMINES AS MODEL SYSTEMS

This work explores the biomimetic potential of [F-18]fluorine for hydr oxy substitution in beta-phenethanolamines as a possible strategy for developing radiotracers for in vivo imaging. Stereospecific syntheses of the two model compounds (1R,2S)-1-[F-18]fluoro-1-deoxyephedrine ([F -18]FDE) and (1S,2S)-1-[F-18]fluoro-1-deoxypseudoephedrine ([F-18]FDP) were achieved in high radiochemical yield (62%, decay corrected) and high specific activity (> 2500 Ci/mmol) by reaction of [F-18]fluoride ion with the appropriate chiral cyclic sulfamidate precursor. Both tra cers exhibited good stability toward metabolic defluorination in vivo. High, homogeneous brain uptake (similar to 8% of injected dose) was o bserved after intravenous injection in mice similar to that reported f or the structurally related analog [C-11]methamphetamine. The 1R,2S is omer (FDE) showed a 3-fold higher concentration of radioactivity in wh ole brain as compared to the 1S,2S isomer (FDP). These results suggest possible employment of this strategy for chiral radiolabeling of biol ogically important phenethanolamines and catecholamines.