Synthesis of (R)-(-)- and (S)-(+)-4-fluorodeprenyl and (R)-(-)- and (S)-(+)-(N- sup 11 C-methyl)-4-fluorodeprenyl and positron emission tomography studies in baboon brain

Journal Article · Sun Jul 01 00:00:00 EDT 1990 · Journal of Medicinal Chemistry; (USA)

DOI:https://doi.org/10.1021/jm00169a034· OSTI ID:6642554

Plenevaux, A; Dewey, S L; Fowler, J S; Guillaume, M; Wolf, A P ^[1]

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1. Brookhaven National Laboratory, Upton, NY (USA)

(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.

• OSTI ID: 6642554
• Journal Information: Journal of Medicinal Chemistry; (USA), Vol. 33:7; ISSN 0022-2623
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BRAIN
POSITRON COMPUTED TOMOGRAPHY
RADIOPHARMACEUTICALS
CHEMICAL PREPARATION
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LABELLING
MOLECULAR STRUCTURE
REAGENTS
STRUCTURE-ACTIVITY RELATIONSHIPS
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DIAGNOSTIC TECHNIQUES
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LABELLED COMPOUNDS
LIGHT NUCLEI
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
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550601* - Medicine- Unsealed Radionuclides in Diagnostics