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N.C.A. 18 F‐labelled norephedrine derivatives via α‐aminopropiophenones
Author(s) -
Ermert J.,
Hamacher K.,
Coenen H. H.
Publication year - 2000
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/1099-1344(200012)43:14<1345::aid-jlcr424>3.0.co;2-n
Subject(s) - chemistry , diastereomer , propiophenone , stereoselectivity , nucleophile , yield (engineering) , nucleophilic substitution , medicinal chemistry , stereochemistry , ketone , organic chemistry , catalysis , materials science , metallurgy
N‐protected 2‐amino‐1‐([ 18 F]fluorophenyl)‐1‐propanones are interesting fluorine‐18 labelled intermediates to synthesize potential PET‐tracers for mapping the adrenergic nervous system of the heart. Several N‐protected α‐aminoalkylarylketones were prepared to examine the direct nucleophilic n.c.a. 18 F‐fluorination of these carbonyl activated precursors. The influence of different protecting groups, the kind of leaving group and the stereoselective reduction of the keto function have been investigated in order to optimize the radiotracer production. It was shown that the 18 F‐substitution 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‐dibenzylamino‐1‐(4‐[ 18 F]fluorophenyl)‐1‐propanol was performed using BH 3 ·THF. The diastereomeric excess was about 80 %. Hydrogenolytical debenzylation was achieved with ammonium formiate in presence of palladium on charcoal to give the 4‐[ 18 F]fluoronorephedrine with a radiochemical yield of 15–20% within a total time of 60 min. Copyright © 2000 John Wiley & Sons, Ltd.