Synthesis of (R)-(-)- and (S)-(+)-4-fluorodeprenyl and (R)-(-)- and (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl and positron emission tomography studies in baboon brain.
Plenevaux, Alain; Dewey, Stephen L.; Fowler, Joanna S.et al.
1990 • In Journal of Medicinal Chemistry, 33 (7), p. 2015-9
[en] (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.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège Brookhaven National Laboratory NY USA
Disciplines :
Radiology, nuclear medicine & imaging
Author, co-author :
Plenevaux, Alain ; Université de Liège - ULiège > Centre de recherches du cyclotron
Dewey, Stephen L.
Fowler, Joanna S.
Guillaume, Marcel
Wolf, Alfred P.
Language :
English
Title :
Synthesis of (R)-(-)- and (S)-(+)-4-fluorodeprenyl and (R)-(-)- and (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl and positron emission tomography studies in baboon brain.
Publication date :
1990
Journal title :
Journal of Medicinal Chemistry
ISSN :
0022-2623
eISSN :
1520-4804
Publisher :
American Chemical Society, Washington, United States - District of Columbia
Volume :
33
Issue :
7
Pages :
2015-9
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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