Asymmetric synthesis of 6-18F-L-FDOPA using chiral Nickel(II) complexes

A new procedure was suggested for asymmetric synthesis of of 6-[ 18 F]fluoro-3,4- L -dihydroxyphenylalanine (6- 18 F- L -FDOPA), an important radiotracer for studies of the dopaminergic system by positron emission tomography (PET). The key step of the synthesis is stochiometric asymmetric alkylation of chiral Ni(II) complexes using 3,4-methylenedioxy-6-[ 18 F]fluorobenzyl bromide as alkylating agent. A series of Ni(II) complexes containing various substituents in the benzyl group were tested. The highest enantiomeric purity of 6- 18 F- L -FDOPA was attained with the complex derived from ( S )- N -(2-benzoylphenyl)-1-(3,4-dichlorobenzyl)-pyrrolidine-2-carboxamide, Ni-DCBPB-Gly, under mild alkylation conditions (CH 2 Cl 2 , 40°C, potassium tert -butylate as base). Such conditions are favorable from the viewpoint of synthesis automation. The radiochemical yield of 6- 18 F- L -FDOPA corrected for the radioactive decay was 10–15% at a synthesis time of 120 min, including purification by semipreparative HPLC. The radiochemical and chemical purity of the product exceeded 99%, and the enantiomeric purity was as high as 95%, meeting the requirements for using 6- 18 F- L -FDOPA in PET practice.