Selectivity of elemental fluorine towards l-tyrosine and l-α-methyltyrosine in acidic media and the syntheses of their [18F]3-fluoro and [18F]3,5-difluoro derivatives

Fluorinated derivatives of l-tyrosine and l-α-methyltyrosine (l-α-MT) are known to be useful tracers for medical imaging with positron emission tomography. Direct fluorination of l-tyrosine and l-α-MT with [18F]F2 in different acidic media show increases in the radio-chemical yield of the 3-fluoro isomers as the acidity of the reaction medium is increased. Lower radiochemical yields and increased production of the 3,5-difluoro isomers of the tyrosine derivatives resulted when solvent mixtures containing BF3 added to anhydrous HF (aHF) were used. Lower yields in BF3/aHF have been studied by use of low-temperature (−70°C) 1H and 13C NMR spectroscopy of l-α-MT, which showed deactivation of the aromatic ring in BF3/aHF. Improved isocratic preparative and analytical HPLC methods for the separation of the fluorinated tyrosine derivatives were also developed. All compounds synthesized in this study were characterized by NMR spectroscopy and mass spectrometry.