Asymmetric Synthesis of L-[β-~(11)C]-3,4-Dihydroxyphenylalanine via the Chiral Ni(II) Complex of the Schiff Base Derived from (S)-o-N-(N′-Benzylprolyl)aminobenzophenone and Glycine (Ni-BPB-Gly)

摘要

A procedure was proposed for asymmetric synthesis of L-[β-~(11)C]-3,4-dihydroxyphenylalanine (L-[β-~(11)C]DOPA), which is a radiotracer used for estimating the density of dopaminergic neurons by positron emission tomography (PET). The procedure involves the use of a new chiral inductor, the nickel complex of the Schiff base derived from (S)-o-N-(N′-benzylprolyl)aminobenzophenone and glycine (Ni-BPB-Gly). The reaction of the asymmetric inductor Ni-BPB-Gly with [α-~(11)C]-3,4-dimethoxybenzyl bromide in the presence of potassium tert-butylate was performed in acetone at 80℃ for 5 min. Decomposition of the resulting diastereomeric complex with 6 M HCl, followed by demethylation of hydroxy groups with concentrated HI, yielded L-DOPA. The radiochemical yield corrected for the ~(11)C decay was 2-16% at the synthesis time of 60-66 min (with an RB-86 robotic system, Anatech). The enantiomeric excess (ee) of L-[β-~(11)C]DOPA varied within 60-98%. The possibility of asymmetric synthesis of L-[β-~(11)C]DOPA was demonstrated for the first time; however, the procedure requires further optimization.