Synthesis of (R)-(-)- and (S)-(+)-4-fluorodeprenyl and (R)-(-)- and (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl and positron emission tomography studies in baboon brain.
(R)-(-)- and (S)-(+)-alpha-methyl-beta-4-(fluorophenyl)-N-methyl-N- propynylethylamine [R)-(-)- and (S)-(+)-4-fluorodeprenyl) were synthesized via the reaction of 4-fluorobenzaldehyde with nitroethane followed by reduction with lithium aluminum hydride to produce racemic 4-fluoroamphetamine, which was resolved by recrystallization with L- or D-N-acetylleucine to yield (R)-(-)-4-fluoroamphetamine or (S)-(+)-4-fluoroamphetamine in greater than 96% enantiomeric excesses and in yields of 42 and 39%, respectively. Alkylation with propargyl bromide gave (R)-(-)- or (S)-(+)-4-fluoronordeprenyl which was reductively methylated (Borch conditions) to produce (R)-(-)- or (S)-(+)-4-fluorodeprenyl. Alkylation of (R)-(-)- or (S)-(+)-4-fluoronordeprenyl with carbon-11 labeled methyl iodide gave (R)-(-)- or (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl in a radiochemical yield of 30-40%. Comparative PET studies of the two labeled enantiomers in baboons showed a significantly lower retention of radioactivity in the striatum for the (S)-(+) enantiomer relative to the (R)-(-) enantiomer.
Plenevaux
A
A
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973.
Dewey
S L
SL
Fowler
J S
JS
Guillaume
M
M
Wolf
A P
AP
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D015394:Molecular Structure; D009928:Organ Specificity; D010215:Papio; D010627:Phenethylamines / Q000138:chemical synthesis*; D012642:Selegiline / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D007202:Indicators and Reagents; D010627:Phenethylamines; C064772:4-fluorodeprenyl; D012642:Selegiline