The synthesis of no-carrier-added DL-4-[18F]fluorodeprenyl via the nucleophilic aromatic substitution reaction.
No-carrier-added DL-alpha-methyl-beta-4-[18F]fluorophenyl-N-methyl-N-propynylethylamin e (DL-4-[18F]fluorodeprenyl) was synthesized via the following 3-step procedure: (1) nucleophilic aromatic substitution by [18F]fluoride on 4-nitrobenzaldehyde to produce 4-[18F]fluorobenzaldehyde (yield 65%); (2) the reaction of 4-[18F]fluorobenzaldehyde with (1-chloro-1-(trimethylsilyl)ethyl)lithium followed by hydrolysis to give 4-[18F]fluorophenylacetone (yield 50%); and (3) reductive alkylation of 4-[18F]fluorophenylacetone with N-methyl-propynylamine in the presence of NaBH3CN (yield 35%) followed by HPLC purification to give a racemic mixture of 4-[18F]fluorodeprenyl. The overall yield was 11% (EOB corrected), the synthesis time was 90 min and the specific activity greater than 0.57 Ci/mumol (end of synthesis). This synthesis approach, the conversion of an aromatic aldehyde to a homologous methyl ketone, extends the flexibility of the nucleophilic aromatic substitution reaction by applying it to the synthesis of radiotracers which do not bear electron-withdrawing activating groups on the aromatic ring. The tissue distribution of DL-4-[18F]fluorodeprenyl in mice at 1, 10 and 60 min was also measured and showed that metabolic defluorination was not significant. Clearance of radioactivity from brain after injection of DL-4-[18F]fluorodeprenyl was more rapid than that previously observed for [11C]L-deprenyl.
Plenevaux
A
A
Liege University, Cyclotron Research Center, Belgium.
Fowler
J S
JS
Dewey
S L
SL
Wolf
A P
AP
Guillaume
M
M
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; D051379:Mice; D015394:Molecular Structure; D012642:Selegiline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; C064772:4-fluorodeprenyl; D012642:Selegiline