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.

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.