Synthesis of stereo (R and S) and geometric (E and Z) isomers of [F-18]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-tyro sine [(E)-FMMT] and its racemic geometric isomer, (Z)-beta-fluoromethylene m-tyrosine [(Z)-FMMT] with [F-18]acetyl hypofluorite ([F-18]AcOF) gave a mi xture of aromatic ring fluorinated products and a pair of diastereomeric pr oducts of addition across the exocyclic double bond. Semipreparative high p erformance liquid chromatography (HPLC) enabled a complete separation and i solation of these products, namely, 6-[F-18]fluoro, 2-[F-18]fluoro, and 2,6 -[F-18]difluoro (E)-FMMT and (Z)-FMMT derivatives, No attempt was made to i solate the individual components of the addition product. Pure racemic 4-[F -18]fluoro-(E)-beta-fluoromethylene-m-tyrosine was also synthesized from a substituted (E)-FMMT precursor involving a fluorodestannylation reaction wi th [F-18]F-2. The availability of stereo (R and S) isomers of 6-[F-18]fluor o and 2 [F-18]fluoro (E)-FMMT and those of the racemic (Z)-FMMT along with 4-[F-18]fluoro-(E)-beta-fluoromethylene-m-tyrosine would now enable a syste matic investigation of the central monoamine oxidase/aromatic amino acid de carboxylase enzyme system with positron emission tomography. NUCL MED BIOL 26;4:359-363, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.