[en] [F-18]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-[F-18]fluoro-4,5-dimethoxybenzyl halide (X = Br, I). The reaction proceeded with high yield (> 90%) at 0 degreesC or room temperature in various solvents such as toluene or dichloromethane. Preparation of the [F-18]alkylating agent on a solid support was developed. After labelling, the labeled [F-18]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-[F-18]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%). (C) Wiley-VCH Verlag GmbH
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège CERMEP Lyon
Disciplines :
Chemistry
Author, co-author :
Lemaire, Christian ; Université de Liège - ULiège > Centre de recherches du cyclotron
Gillet, Steve
Guillouet, Stéphane
Plenevaux, Alain ; Université de Liège - ULiège > Centre de recherches du cyclotron
Aerts, Joël ; Université de Liège - ULiège > Centre de recherches du cyclotron
Luxen, André ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse - Centre de recherches du cyclotron
Language :
English
Title :
Highly enantioselective synthesis of no-carrier-added 6-[18F]Fluoro-L-dopa by chiral phase-transfer alkylation
Publication date :
28 June 2004
Journal title :
European Journal of Organic Chemistry
ISSN :
1434-193X
eISSN :
1099-0690
Publisher :
Wiley VCH Verlag, Weinheim, Germany
Issue :
13
Pages :
2899-2904
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
E. S. Garnett, G. Firnau, C. Nahmias, Nature 1983, 305, 137-138.
M. E. Phelps, Annu. Rev. Nucl. Part. Sci. 2002, 52, 303-338.
A. Luxen, M. Guillaume, W. P. Melega, V. W. Pike, O. Solin, R. Wagner, Nucl. Med. Biol. 1992, 19, 149-158.
E. F. de Vries, G. Luurtsema, M. Brüssermann, P. H. Elsinga, W. Vaalburg, Appl. Radiat. Isot. 1999, 51, 389-394.
C. Lemaire, P. Damhaut, A. Plenevaux, D. Comar, J. Nucl. Med 1994, 35, 1996-2002.
D. Seebach, E. Dziadulewicz, L. Behrendt, S. Cantoreggi, R. Fitzi, Liebigs Ann. Chem. 1989, 12, 1215-1232.
K. Maruoka, T. Ooi, Chem. Rev. 2003, 103, 3013-3028.
M. J. O'Donnell, W. D. Bennett, S. Wu, J. Am. Chem. Soc. 1989, 111, 2353-2355.
E. J. Corey, F. Xu, M. C. Noe, J. Am. Chem. Soc. 1997, 119, 12414-12415.
E. J. Corey, M. C. Noe, F. Xu, Tetrahedron Lett. 1998, 39, 5347-5350.
B. Lygo, P. G. Wainnwright, Tetrahedron Lett. 1997, 38, 8595-8598.
C. Lemaire, P. Damhaut, A. Plenevaux, R. Cantineau, L. Christiaens, M. Guillaume, Appl. Radiat. Isot. 1992, 43, 485-494.
R. Iwata, C. Pascali, A. Bogni, G. Horvath, Z. Kovaacs, K. Yanai, T. Ido, Appl. Radiat. Isot. 2000, 52, 87-92.
S. V. Ley, I. R. Baxendale, R. N. Bream, P. S. Jackson, A. G. Leach, D. A. Longbottom, M. Nesi, J. S. Scott, R. I. Storer, S. J. Taylor, J. Chem. Soc., Perkin Trans. 1 2000, 3815-4195.
C. Lemaire, P. Damhaut, B. Lauricella, C. Mosdzianowski, J.-L. Morelle, M. Monclus, J. Van Naemen, E. Mulleneers, J. Aerts, A. Plenevaux, C. Brihaye, A. Luxen, J. Labelled Compd. Rad. 2002, 45, 435-447.
M. J. O'Donnell, F. Delgado, C. Hostettler, R. Schwesinger, Tetrahedron Lett. 1998, 39, 8775-8778.
C. Brihaye, C. Lemaire, Ph. Damhaut, A. Plenevaux, D. Comar, J. Labelled Compd. Rad. 1994, 35, 160-162.