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

Various [F-18]fluoro aromatic alpha-methyl-L-amino acids 11 have been synthesized with high enantiomeric purity tee > 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 [F-18]fluoro aromatic aldehydes 12 obtained were easily converted to the corresponding [F-18]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 [F-18]fluoro-alpha-methyl amino acid analogs with radiochemical yields of 10% (End of Bombardment, EOB) after a synthesis time of 120 min. The corresponding [F-19]fluorinated amino acids 4 and [F-19]fluoro intermediates were also prepared. (C) 1997 Elsevier Science Ltd.