ASYMMETRIC-SYNTHESIS OF C-11 LABELED L-AMINO AND D-AMINO ACIDS BY ALKYLATION OF IMIDAZOLIDINONE DERIVATIVES

Alanine and phenylalanine have been labelled in the 3-position, and 2-aminoadipic acid in the 6-position, with the short-lived positron-emitting radionuclide C-11 (t(1/2) = 20.3 min). (R)- and (S)-2-tert-butyl-1-tert-butyloxycarbonyl-3-methyl-4-imidazolidinone were alkylated with [C-11]methyl iodide, [alpha-C-11]benzyl iodide or 4-iodobutyro[C-11]nitrile, prepared in multi-step syntheses starting from [C-11]carbon dioxide. 3-C-11-Labelled L- and D-alanine and phenylalanine were obtained after acidic hydrolysis in 75 and 30% radiochemical yields (decay-corrected) within 25 and 50 min, respectively. The radiochemical purities were higher than 98%. After a two-step hydrolysis procedure, L- and D-2-amino[6-C-11]adipic acid were obtained in 20-25% radiochemical yield (decay-corrected) within 45 min with a radiochemical purity of 85%. The enantiomeric purities were 98% for alanine and phenylalanine and >96% for 2-aminoadipic acid. In a typical synthesis, 385 MBq of [3-C-11]alanine were obtained, starting with 1.2 GBq [C-11]carbon dioxide, with a synthesis time of 25 min.