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Highly Enantioselective Synthesis of No‐Carrier‐Added 6‐[ 18 F]Fluoro‐ L ‐dopa by Chiral Phase‐Transfer Alkylation
Author(s) -
Lemaire Christian,
Gillet Steve,
Guillouet Stéphane,
Plenevaux Alain,
Aerts Joël,
Luxen André
Publication year - 2004
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200400059
Subject(s) - chemistry , alkylation , enantioselective synthesis , hydrobromic acid , organic chemistry , cyanation , nuclear chemistry , catalysis
[ 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‐dimethoxybenzyl halide (X = Br, I). The reaction proceeded with high yield (> 90%) at 0 °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]fluoroveratraldehyde was trapped on a t C18 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%). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)