title: Synthesis of stereo (R and S) and geometric (E and Z) isomers of [18F]fluoro-beta-fluoromethylene-m-tyrosine derivatives: in vivo probes of central dopaminergic function.
abstract: Fluorination of pure R and S enantiomers of (E)-beta-fluoromethylene-m-tyrosine [(E)-FMMT] and its racemic geometric isomer, (Z)-beta-fluoromethylene-m-tyrosine [(Z)-FMMT] with [18F]acetyl hypofluorite ([18F]AcOF) gave a mixture of aromatic ring fluorinated products and a pair of diastereomeric products of addition across the exocyclic double bond. Semipreparative high performance liquid chromatography (HPLC) enabled a complete separation and isolation of these products, namely, 6-[18F]fluoro, 2-[18F]fluoro, and 2,6-[18F]difluoro (E)-FMMT and (Z)-FMMT derivatives. No attempt was made to isolate the individual components of the addition product. Pure racemic 4-[18F]fluoro-(E)-beta-fluoromethylene-m-tyrosine was also synthesized from a substituted (E)-FMMT precursor involving a fluorodestannylation reaction with [18F]F2. The availability of stereo (R and S) isomers of 6-[18F]fluoro and 2-[18F]fluoro (E)-FMMT and those of the racemic (Z)-FMMT along with 4-[18F]fluoro-(E)-beta-fluoromethylene-m-tyrosine would now enable a systematic investigation of the central monoamine oxidase/aromatic amino acid decarboxylase enzyme system with positron emission tomography.
authors.affiliation: Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095, USA.
authors.forename: G
authors.initials: G
authors.lastname: Lacan
authors.forename: N
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: J R
authors.initials: JR
authors.lastname: Barrio
mesh_terms: D001921:Brain / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis*; D013237:Stereoisomerism; D014055:Tomography, Emission-Computed; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D005462:Fluorine Radioisotopes; D008996:Monoamine Oxidase Inhibitors; D014443:Tyrosine; C046880:beta-fluoromethylene-3-tyrosine; D004298:Dopamine