[en] Asymmetric nucleophilic synthesis of 6-[F-18]fluoro-L-dopa was investigated in order to reach an enantiomeric excess of close to 100% of the L form of this amino acid. The radiochemical synthesis required [F-18]fluoride as fluorinating agent and regioselective nucleophilic substitution of commercially available 6-nitroveratraldehyde. The [F-18]fluorobenzaldehyde thus obtained was easily converted to the corresponding 2-[F-18]fluoro-4,5-dimethoxybenzyl bromide. This alkylating agent was added to the lithium enolates of 1-(S)-(-)camphor imine of t-butyl glycinate (1) and (S)-(-)- 1 -Boc-2-t-butyl-3-methyl-4-imidazolidinone [(S)- Boc-BMI] (2) in order to compare the enantiomeric excess of the L form obtained in each case with these two chiral inductors. The L-isomer of fluorodopa was isolated after H1 hydrolysis and HPLC purification in 5-10% radiochemical yield (decay corrected). The overall synthesis time was of 110 min. Through this synthetic pathway, the L-isomer of fluorodopa was obtained in 83% e.e with 1 and 96% e.e with 2 respectively, as determined by chiral HPLC. A practical three step preparative scale synthesis of 6-[F-19]fluoro-D,L-dopa is also presented.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Radiology, nuclear medicine & imaging Chemistry
Author, co-author :
Lemaire, Christian ; Université de Liège - ULiège > Centre de recherches du cyclotron
Plenevaux, Alain ; Université de Liège - ULiège > Centre de recherches du cyclotron
Cantineau, Robert
Christiaens, Léon
Guillaume, Marcel
Comar, Dominique
Language :
English
Title :
NUCLEOPHILIC ENANTIOSELECTIVE SYNTHESIS OF 6-[F-18]FLUORO-L-DOPA VIA 2 CHIRAL AUXILIARIES
Publication date :
1993
Journal title :
Applied Radiation and Isotopes
ISSN :
0969-8043
Publisher :
Pergamon Press, Oxford, United Kingdom
Volume :
44
Issue :
4
Pages :
737-744
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Adam, Jivan (1988) Synthesis and purification of l-6-[18F]fluorodopa. Appl. Radiat. Isot. 39:1203.
Adam, Grierson, Ruth, Jivan (1986) Reaction of [18F]acetyl hypofluorite with derivatives of dihydroxyphenylalanine: synthesis of l-[18F]6-fluorodopa. Appl. Radiat. Isot. 37:877.
Adam, Ruth, Grierson, Abeysekera, Pate (1986) Routine synthesis of l-[18F]6-fluorodopa with fluorine-18 acetyl hypofluorite. J. Nucl. Med. 27:1462.
Chaly, Diksic (1986) High yield synthesis of 6-[18F]fluoro-l-dopa by regioselective fluorination of protected l-dopa with [18F]acetylhypofluorite. J. Nucl. Med. 27:1896.
Chirakal, Firnau, Couse, Garnett (1984) Radiofluorination with 18F-labelled acetyl hypofluorite: [18F]l-6-fluorodopa. Int. J. Appl. Radiat. Isot. 35:651.
Chirakal, Firnau, Garnett (1986) High yield synthesis of 6-[18F]fluoro-l-dopa. J. Nucl. Med. 27:417.
Diksic, Farrokhzad (1985) New synthesis of fluorine-18-labelled 6-fluoro-l-dopa by cleaving the carbon-silicon bond with fluorine. J. Nucl. Med. 26:1314.
Ding, Shiue, Fowler, Wolf, Plenevaux (1990) No-carrier-added (NCA) aryl[18F]-fluorides via the nucleophilic aromatic substitution of electron-rich aromatic rings. J. Fluorine Chem. 48:189.
Fasth, Malmborg, Langström (1991) Two synthetic routes for the asymmetric synthesis of [β-11C]amino acids with high enantiomeric purities. J. Labelled Compds Radiopharm. 30:401.
Firnau, Chirakal, Sood, Garnett (1980) Aromatic fluorination with xenon difluoride l-34-dihydroxy-6-fluoro-phenylalanine. Canadian Journal of Chemistry 58:1449.
Firnau, Chirakal, Garnett (1984) Aromatic radiofluorination with [18F]fluorine gas: 6-[18F]fluoro-l-dopa. J. Nucl. Med. 25:1228.
Firnau, Garnett, Chirakal, Sood, Nahmias, Schrobilgen (1986) [18F]fluoro-l-dopa for the in vivo study of intracerebral dopamine. Appl. Radiat. Isot. 37:669.
Fitzi, Seebach (1988) Resolution and use in α-amino acid synthesis of imidazolidinone glycine derivatives. Tetrahedron 44:5277.
Furlano, Kirk (1986) An improved synthesis of 4-fluoroveratrole. Efficient route to 6-fluoroveratraldehyde and 6-fluoro-d,l-dopa. J. Org. Chem. 51:4073.
Forni, Moretti, Torre (1978) Absolute configuration at chiral nitrogen in oxiziridines configurational correlation by NMR spectroscopy in optically active solvating agents. Tetrahedron Letters 2941.
Haemers, Mishra, Van Assche, Bollaert (1989) Asymmetric synthesis of amino acids by enantio and diastereodifferentiating reactions. Die Pharmazie 44:97.
Lemaire, Guillaume, Christiaens (1989) Asymmetric synthesis of 6-[18F]fluoro-l-dopa via NCA nucleophilic radiofluorination. J. Nucl. Med. , (Abstract); 30:752.
Lemaire, Guillaume, Cantineau, Plenevaux, Christiaens (1990) No-carrier-added regioselective preparation of 6-[18F]fluoro-l-dopa. J. Nucl. Med. 31:1237.
Lemaire, Guillaume, Cantineau, Plenevaux, Christiaens (1991) An approach to the asymmetric synthesis of l-6-[18F]-fluorodopa via nca nucleophilic fluorination. Appl. Radiat. Isot. 42:629.
Lemaire, Guillaume, Damhaut, Cantineau, Plenevaux, Christiaens (1992) Synthesis of Fluorine-18 substituted aromatic aldehydes and benzylbromides, new intermediates for n.c.a. fluorinations. Appl. Radiat. Isot. 43:485.
Lloyd, Platt (1969) A convenient synthesis of 5-oxazolones, 2-phenyl-5-oxazolone. Org. Prep. Proc. 1:217.
Luxen, Barrio, Bida, Satyamurthy (1986) Regioselective radiofluorodemercuration. A simple, high yield synthesis of 6-[18F]fluorodopa. J. Labelled Compds Radiopharm. , (Abstract); 23:1066.
Luxen, Perlmutter, Bida, Van Moffaerts, Cook, Satyamurthy, Phelps, Barrio (1990) Remote, semiatomated production of 6-[18F]fluoro-l-dopa for human studies with PET. Appl. Radiat. Isot. 41:275.
Luxen, Guillaume, Melega, Pike, Solin, Wagner (1992) Production of 6-[18F]fluoro-l-dopa and its metabolism In Vivo—a critical review. Appl. Radiat. Isot. 19:149.
McIntosh, Mishra (1986) Alkylation of camphor imines of glycinates Diastereoselectivity as a function of electronic factors in the alkylating agent. Canadian Journal of Chemistry 64:726.
McIntosh, Leavitt, Mishra, Cassidy, Drake, Chadha (1988) Diastereoselective alkylation guided by electrophile-nucleophile π-interactions. The Journal of Organic Chemistry 53:1947-1952.
Pedersen, Scheibye, Nilsson, Lawesson (1978) Studies on organophosphorus compounds XX. Syntheses of thioketones. Bull. Soc. Chim. Belg. 87:223.
Scheibye, Pedersen, Lawesson (1978) Studies on organophosphorus compounds XXI. The dimer of p-methoxyphenylthionophosphine sulfide as thiation reagent. A new route to thiocarboxamides. Bull. Soc. Chim. Belg. 87:229.
Seebach, Dziadulewicz, Behrendt, Cantoreggi, Fitzi (1989) Synthesis of nonproteinogenic (R)- or (S)-amino acids analogues of phenylalanine isotopically labelled and cyclic amino acids from tert-butyl 2(t-butyl)-3-methyl-4-oxo-1-imidazolidinecarboxylate. Liebigs Annalen der Chemie 12:1215.
Shahak, Sasson (1973) Preparation of substituted camphorimines. Synthesis 535:1973.
Taylor, Platt (1969) A convenient synthesis of 5-oxazolones, 2-phenyl-5-oxazolone. Org. Prep. Proc. 1:217-219.
Williams Synthesis of Optically Active α-Amino Acids , Pergamon Press, Oxford; 1989, 1-133.
