With regard to a stereoselective reduction of the carbonyl group, several N-protected -aminopropiophenones were prepared as model compounds in order to examine the influence of the protecting group on the radiochemical yield of a ¹⁸F-for-X substitution (X= F, Cl, NO₂, +N(CH₃)₃).

Good radiochemical yields could be achieved using the N-dibenzyl- or acetyl-protected compounds. The para-position of the leaving group provided higher radiochemical yields than the ortho-position in the case of the ¹⁸F-for-¹⁹F substitution. It has been shown that the less basic oxalate/cryptate system does not increase the radiochemical yields.

¹⁸F-Fluorination of the nitro compound failed because the precursor was not stable under labelling conditions. The best results of n.c.a. ¹⁸F-fluorination were obtained using the trimethylammonium leaving group (X = ⁺N(CH₃)₃) in para-position (RCY about 50 %), however, a selective quaternisation of the dimethylaniline group was only possible when using the N,N-dibenzylated derivative.

The n.c.a. labelling of 4-[¹⁸F]fluoronorephedrine and 4-[¹⁸F]fluorometaraminol was finally performed via ¹⁸F-for-N(CH₃)₃ substitution on 4-(2-N,N- dibenzylaminopropionyl)phenyl-1-N,N,N-trimethyl- ammonium triflate and 4-(2-N,N-dibenzylaminopropionyl)-2-benzyloxyphenyl-1-N,N,N-trimethyl- ammonium triflate, respectively. The precursor of 4-[¹⁸F]fluorometaraminol has been synthesized in an eleven step reaction sequence and characterized with IR and ¹H-NMR.

The formation of the threo-isomer of n.c.a. 4-[¹⁸F]fluoronorephedrine was achieved by reduction of n.c.a. 2-N,N-dibenzylamino-1-(4-[¹⁸F]fluorophenyl)propan-1-on using sodium borohydride in methanol as reducing agent. The radiochemical yield was about 20% after hydrogenolytical debenzylation using ammonium formate and palladium on charcoal.

The formation of the erythro-isomer of 4-[¹⁸F]fluoronorephedrine and 4- [¹⁸F]fluorometaraminol was accomplished with BH₃ THF in the presence of 2-N,N-dibenzylamino-1-(4- [¹⁸F]fluoro- phenyl)propan-1-on and 2-N,N-dibenzylamino-1-(4-[¹⁸F]fluoro-3-benzyloxyphenyl)propan-1-on respectively. The ratio of erythro- to threo-isomer was 4:1. The radiochemical yield of erythro-4- [¹⁸F]fluoronorephedrine and erythro-4-[¹⁸F]fluorometaraminol after deprotection using ammonium formate and palladium on charcoal was 15-20 ;#37; with a specific activity of about 74 GBq/[my]mol (2 Ci/[my]mol).

The new synthetic pathway makes it possible to synthesize these labelled sympathomimetics no carrier added and to investigate the presynaptic adrenergic nervous system of the heart using positron emission tomography.