Highly Enantioselective Synthesis of No-Carrier-Added 6-[18F]Fluoro-L-dopa by Chiral Phase-Transfer Alkylation

摘要

[~(18)F]Fluoro-L-dopa,an important radiopharmaceutical for positron emission tomography (PET),has been synthesized using a phase-transfer alkylation reaction.A chiral quaternary ammonium salt derived from a Cinchona alkaloid served as phase-transfer catalyst for the enantioselective alkylation of a glycine derivative.The active methylene group of this Schiff-base substrate was deprotonated with cesium hydroxide and rapidly alkylated by the 2-[~(18)F]fluoro-4,5-di-methoxybenzyl halide (X=Br,I).The reaction proceeded with high yield (> 90%)at 0 deg C or room temperature in various solvents such as toluene or dichloromethane.Preparation of the [~(18)F]alkylating agent on a solid support was developed.After labelling,the labeled [~(18)F]fluoroveratralde-hyde was trapped on a ~tC 18 cartridge and then converted on the cartridge into the corresponding benzyl halide derivatives by addition of aqueous sodium borohydride and gaseous hydrobromic or-iodic acid.Hydrolysis and purification by preparative HPLC made 6-[~(18)F]fluoro-L-dopa ready for human injection in a 25-30% decay-corrected radiochemical yield in a synthesis time of.100 min.The product was found to be chemically,radiochemically and enantiomerically pure (ee > 95%).