The Efficient Preparation of Radiolabeled Aromatic Amino Acids via Cu-Mediated Radiofluorination using Ni-complexes

Ziel/Aim: The aim of this work was to develop a procedure for the preparation of F-18-labeled aromatic amino acids (AAA) via alcohol-enhanced Cu-mediated radiofluorination using Ni-BPX auxiliaries as easily-removable dual-protecting groups. Methodik/Methods: The Bpin-substituted precursors of radiofluorinated AAA and α-Me-AAA were prepared by alkylation of (S)-Ni-BPB-Gly and (S)-Ni-BPA-(RS)-Ala with the corresponding Bpin-substituted benzyl bromides. Radiolabeling was carried out according to the protocol for alcohol-enhanced 1 Cu-mediated radiofluorination as follows: F-18-F - was loaded onto a QMA-cartridge which was subsequently washed with MeOH; F-18-F - was eluted with Et 4 NHCO 3 to a solution of Cu(py) 4 (OTf) 2 and precursor in DMF/nBuOH (2:1), and the reaction mixture was stirred under air at 110 °C for 10 min. Evaporation of the DMA/nBuOH was followed by deprotection using 12 M HCl at 110 °C for 15 min. The acidic solution was evaporated and the tracer was isolated by HPLC. Ergebnisse/Results: Ni complexes containing 2 – 4-F-18-FPhe, 2 – 4-aMe-F-18-FPhe, 6-F-18-FMT, aMe-6-F-18-FMT, 4-F-18-FTrp and 2-Me-F-18-FTyr residues were obtained in RCCs of 50 – 95%. The purified tracers were isolated in n.d.c 15 – 25% RCYs in excellent radiochemical and enantiomeric purity. Radiosyntheses of 4-F-18-FPhe and 4-F-18-FTrp were implemented to an automated module furnishing tracers in n.d.c RCYs of 25% and 17%, respectively, within 75 – 80 min. Schlussfolgerungen/Conclusions: Alcohol-enhanced Cu-mediated radiofluorination of BPin substituted Ni-BPX-AAA complexes is a simple, yet powerful method for the fast production of structurally diverse radiolabeled AAAs and alpha-methyl substituted AAAs. The attractiveness of the procedure is highlighted by the accessibility of radiolabeling precursors, high RCYs and easy implementation to an automated module. Literatur/References: [1] Zichler, J., Niklas, K., Modemann, D., Neumaier, B., Zlatopolskiy, B.; Chemistry – A European Journal, 2017, 23, 3251 – 3256