title: The synthesis of (R)- and (S)-[N-methyl-11C]beta, beta-difluoromethamphetamine for the investigation of the binding mechanism of biogenic amines in vivo.
abstract: In an attempt to elucidate the contribution of the extent of nitrogen protonation on the in vivo binding of methamphetamine in the brain, the enantiomers of [N-methyl-11C]beta, beta-difluoroamphetamine (4) were prepared for use in positron emission tomography (PET) studies. Thus, the enantiomers of beta, beta-difluoroamphetamine were prepared from trans-beta-methylstyrene, via bromination, conversion into the azirine, fluorination and resolution as the tartrate salts. (R)- and (S)-beta, beta-difluoroamphetamine (3) were then each labelled with carbon-11 (tt/2 = 20.4 min) by N-methylation of the corresponding homochiral beta, beta-difluoroamphetamine with [11C]methyl iodide. The labelled products were each synthesised, purified and formulated in 35 min, starting from [11C]carbon dioxide in 15-16% decay-corrected radiochemical yield, with a radiochemical purity of > 99% and specific radioactivity of 50-150 GBq mumol-1 at end of synthesis.
authors: PET Centre, Aarhus University Hospital, Denmark. nic@pet.auh.dk
authors: N M
authors: NM
authors: Gillings
authors: A D
authors: AD
authors: Gee
authors: O
authors: O
authors: Inoue
mesh_terms: D001665:Binding Sites; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D007553:Isotope Labeling; D007700:Kinetics; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D001679:Biogenic Amines; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; C118516:beta,beta-difluoromethamphetamine; D008694:Methamphetamine