NO-CARRIER-ADDED ASYMMETRIC-SYNTHESIS OF ALPHA-METHYL-ALPHA-AMINO ACIDS LABELED WITH F-18

Various [F-18]fluoro aromatic alpha-methyl-L-amino acids 11 have been synthesized with high enantiomeric purity tee > 97%). These new radiop harmaceuticals for Positron Emission Tomography (PET), potential inhib itors of enzymatic functions, were regiospecifically labelled by nucle ophilic substitution on trimethylammoniumbenzaldehyde triflate precurs ors 9. The [F-18]fluoro aromatic aldehydes 12 obtained were easily con verted to the corresponding [F-18]fluorobenzyl halides [13 (X = I)]. A fter alkylation of the lithium enolate of t-Boc-2-tert-butyl-3,5-dimet hyl-imidazolidin-4-one 2, the adducts were cleaved to give, after HPLC purification, various [F-18]fluoro-alpha-methyl amino acid analogs wi th radiochemical yields of 10% (End of Bombardment, EOB) after a synth esis 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.