NO-CARRIER-ADDED (NCA) ARYL [F-18] FLUORIDES VIA THE NUCLEOPHILIC AROMATIC-SUBSTITUTION OF ELECTRON-RICH AROMATIC RINGS

Nucleophilic aromatic substitution by [18F]fluoride ion has been demonstrated on rings containing electron donating groups in addition to the necessary electron withdrawing and leaving groups. The reaction of 18F- with a series of aromatic nitro aldehydes having protected hydroxyl substituents on the ring was studied. The reactivity of the aromatic ring towards nucleophilic substitution to give 18F-labeled aromatic fluoroaldehyde derivatives is correlated with electron density at the reaction center. The effect of a number of protected hydroxyl substituents is reported. 13C-NMR was used as a sensitive probe for the changes in electron distribution at the ring carbon atoms. Radiochemical yield correlates with ppm values at the reaction center. This methodology has been applied to the synthesis of no-carrier-added (NCA) 6-[18F]fluoro-L-DOPA. The extention of this strategy to the syntheses of other labeled pharmaceuticals appears promising. © 1990.