No-carrier-added asymmetric synthesis of α-methyl-α-amino acids labelled with fluorine-18

Abstract Various [ 18 F]fluoro aromatic α-methyl- l -amino acids 11 have been synthesized with high enantiomeric purity (ee > 97%). These new radiopharmaceuticals for Positron Emission Tomography (PET), potential inhibitors of enzymatic functions, were regiospecifically labelled by nucleophilic substitution on trimethylammoniumbenzaldehyde triflate precursors 9 . The [ 18 F]fluoro aromatic aldehydes 12 obtained were easily converted to the corresponding [ 18 F]fluorobenzyl halides [ 13 (X = I)]. After alkylation of the lithium enolate of (2S,5S)-1- tert -Boc-2- tert -butyl-3,5-dimethyl-imidazolidin-4-one 2 , the adducts were cleaved to give, after HPLC purification, various [ 18 F]fluoro-α-methyl amino acid analogs with radiochemical yields of 10% (End of Bombardment, EOB) after a synthesis time of 120 min. The corresponding [ 19 F]fluorinated amino acids 4 and [ 19 F]fluoro intermediates were also prepared.