NCA F-18-labelled norephedrine derivatives via alpha-aminopropiophenones

N-protected 2-anlino-1-([F-18]fluorophenyl)-1-propanones are interesting fl uorine-18 labelled intermediates to synthesize potential PET-tracers for ma pping the adrenergic nervous system of the heart. Several N-protected alpha -aminoalkylarylketones were prepared to examine the direct nucleophilic n. c.a. F-18-fluorination of these carbonyl activated precursors. The influenc e of different protecting groups, the kind of leaving group and the stereos elective reduction of the keto function have been investigated in order to optimize the radiotracer production. It was shown that the F-18-substitutio n of the para-trimethylammonium group, e.g. of N-dibenzylated propiophenone , leads to radiochemical yields of up to 60%. The stereoselective reduction of the carbonyl function with formation of the n.c.a. erythro 2-N,N-dibenz ylamino-1-(4-[F-18]fluorophenyl)-1-propanol was performed using BH3. THF. T he diastereomeric excess was about 80%. Hydrogenolytical debenzylation was achieved with ammonium formiate in presence of palladium on charcoal to giv e the 4-[F-18]fluoronorephedrine with a radiochemical yield of 15-20% withi n a total time of 60 min.