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| Home > Publications database > The efficient preparation of radiolabeled aromatic amino acids via Cu‐mediated radiofluorination of Ni‐complexes |
| Journal Article | FZJ-2020-00177 |
; ; ; ; ;
2019
Wiley
New York, NY [u.a.]
Abstract: Objectives: The aim of this work was to develop a versatile procedure for the preparation of 18F‐labeled aromatic amino acids (AAA) via alcohol‐enhanced Cu‐mediated radiofluorination using Ni‐BPX auxiliaries as easily‐removable dual‐protecting group functionalities. Additionally, the use Ni‐BPA‐Ala complexes were investigated in order to access a number of synthetically challenging α‐Me‐AAA tracers. Furthermore, the implementation of the radiosynthetic methods into automated modules was carried out in order to facilitate the production of these AAA tracers for biological evaluation.Methods: The Bpin‐substituted precursors of radiofluorinated AAAs and α‐Me AAAs 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 Cu‐mediated radiofluorination as follows:1 [18F]F‐ was loaded onto a QMA‐cartridge which was subsequently washed with MeOH; [18F]F‐ was eluted with Et4NHCO3, solvent was evaporated, the residue was taken up in 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. The evaporation of the DMA/nBuOH was followed by deprotection using 12 M HCl at 110 °C for 15 min. Finally, the desired tracers were isolated by semi‐preparative HPLC.Results: The appropriate BPin‐substituted Ni‐BPX‐AAA complexes were prepared from commercially available materials in 10–72% yield over 1–4 steps. Radiolabeled Ni complexes containing 2–4‐[18F]FPhe, 2–4‐aMe‐[18F]FPhe, 6‐[18F]FMT, aMe‐6‐[18F]FMT, 4‐[18F]FTrp and 2‐[18F] FTyr residues were synthesized in RCCs of 50–95%. The purified tracers were isolated in n.d.c RCYs of 15–40% and in excellent radiochemical and enantiomeric purity. Radiosyntheses of 3‐[18F]FPhe, 4‐[18F]FPhe and 4‐[18F]FTrp were implemented to an automated module furnishing tracers in n.d.c RCYs of 10%, 15% and 17%, respectively, within 75–80 min.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 α‐methyl substituted AAAs. The attractiveness of the procedure is highlighted by the accessibility of radiolabeling precursors, high RCYs and easy implementation into an automated module.
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