Decarbonylation of multi-substituted [18F]benzaldehydes for modelling syntheses of 18F-labelled aromatic amino acids

For F-18-labelling of aromatic amino acids such as tyrosine and DOPA simple and efficient procedures have been under development for quite a while. The direct introduction of F-18 using [F-18]fluoride can principally be realized by nucleophilic aromatic substitution (SNAr). However, this requires the presence of an appropriate leaving group and an auxiliary substituent, which is able to reduce the electron density of the benzene ring. Furthermore, this auxiliary substituent should be removable easily after the introduction of F-18. The electron-withdrawing formyl substituent meets both requirements. It facilitates nucleophilic attack in the ortho and/or para position and is easily removed in a decarbonylation reaction mediated by Wilkinson's catalyst (RhCl(PPh3)(3)). In order to evaluate the reaction conditions for a possible synthesis of 2-[F-18]fluoro-5-hydroxyphenylalanine ([F-18]-m-tyrosine), 2-[F-18(n)]fluoro-4-hydroxyphenylalanine ([F-18]-p-tyrosine) or 2-[F-18]fluoro-4,5-hydroxyphenytalanine ([F-18]FDOPA), the dependence of the decarbonylation reaction on solvent, temperature, reaction time and catalyst concentration was studied using appropriate model compounds. Optimum yields of 81 %, 89% and 88% could be achieved using benzonitrile as solvent and 2 M equivalents of RhCl(PPh3)(3) (based on labelling precursor) at 150 degrees C reaction temperature within 20min reaction time for compounds modelling [F-18]-m-tyrosine, [F-18]-p-tyrosine and [F-18]FDOPA, respectively. (c) 2007 Elsevier Ltd. All rights reserved.