Enantiospecific synthesis of 2-[18F]fluoro-l-phenylalanine and 2-[18F]fluoro-l-tyrosine by isotopic exchange

Abstract

2-[¹⁸F]Fluoro-L-phenylalanine and 2-[¹⁸F]fluoro-L-tyrosine have been developed as promising radiopharmaceuticals for molecular imaging using positron emission tomography (PET). However, the lack of a convenient radiosynthetic pathway has limited their practical use. In this work a new three-step nucleophilic synthesis of these compounds starting from [¹⁸F]fluoride is described. Corresponding precursors (1a and 1b) were ¹⁸F-fluorinated by isotopic exchange, followed by the removal of an activating formyl group with Rh(PPh₃)₃Cl and subsequent hydrolysis of protecting groups in acidic medium. All reactions were carried out using both conventional and microwave heating. Conventional heated reactions yielded the desired products 2-[¹⁸F]Fphe and 2-[¹⁸F]Ftyr in 43% and 49% whereas radiochemical yields of 34% and 43%, respectively, were obtained when they were heated by microwaves. Under optimized conditions the enantiomeric purity was ≥94% for both radiopharmaceuticals.