Enantioselective syntheses of no-carrier-added (nca) (S)-4-chloro-2[F-18]fluorophenylalanine and (S)-(alpha-methyl)-4-chloro-2[F-18]fluorophenylalanine

(S)-4-Chloro-2-fluorophenylalanine and (8)-(alpha-methyl)-4-chloro-2-fluorophenylalanine were synthesized and labeled with no carrier added (n.c.a.) fluorine-18 through a radiochemical synthesis relying on the highly enantioselective reaction between 4-chloro-2-[F-18]fluorobenzyl iodide and the lithium enolate of (2S)-1-(tert-butyloxycarbonyl)-2-(tert-butyl)-3-methyl-1,3-imidazolidine-4-one for (S)-4-chloro-2-[F-18]fluorophenylalanine and (2S,5S)-1-(tert-butyloxycarbonyl)-2-(tert-butyl)-3,5-dimethyl-1,3-imidazolidine-4-one for (S)-(alpha-methyl)-4-chloro-2-[F-18] fluorophenylalanine. Quantities of about 20-25 mCi were obtained at the end of synthesis, ready for injection after hydrolysis and high performance liquid chromatography (HPLC) purification, with a radiochemical yield of 17%-20% corrected to the end of bombardment after a total synthesis time of 90-105 min from [F-18]fluoride. The enantiomeric excesses were shown to be 97% or more for both molecules without chiral separation and the radiochemical and chemical purities were 98% or better.