6-[18F]Fluoro-L-DOPA by radiofluorodestannylation: a short and simple synthesis of a new labelling precursor

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 41; no. 2; pp. 105 - 114
• Main Authors: Dolle, Frédéric, Demphel, Stéphane, Hinnen, Françoise, Fournier, Denis, Vaufrey, Françoise, Crouzel, Christian
• Format: Journal Article
• Language: English
• Published: Chichester John Wiley & Sons, Ltd 01.02.1998; Wiley
• Subjects: 18F; 6-[18F]fluoro-L-DOPA; Aliphatic compounds; Biochemical Research Methods; Biochemistry & Molecular Biology; Biological and medical sciences; Chemistry; Chemistry, Analytical; Chemistry, Medicinal; Contrast media. Radiopharmaceuticals; Exact sciences and technology; F-18; fluorine-18; L-DOPA; labelling precursor; Life Sciences & Biomedicine; Medical sciences; Organic chemistry; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Preparations and properties; Science & Technology; fluorine-18; 6-[F-18]fluoro-L-DOPA; RADIOFLUORINATION; F-18 ACETYL HYPOFLUORITE; L-DOPA; labelling precursor; L-6-FLUORODOPA; FLUORINATION; DOPA; F-18; 18F; HIGH-YIELD SYNTHESIS; α-Aminoacid; Fluorine Isotopes; Enantioselectivity; Fluorine 18; Radiolabelling; Regioselectivity; Scintigraphic agent; Benzenic compound; Levodopa; Chemical synthesis; Diphenols
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/(SICI)1099-1344(199802)41:2<105::AID-JLCR65>3.0.CO;2-H

This paper describes a short and simple synthesis of a new fully protected stannylated precursor, namely N‐(tert‐butoxycarbonyl)‐3,4‐di(tert‐butoxycarbonyloxy)‐6‐trimethylstannyl‐L‐phenylalanine ethyl ester, for the preparation of 6‐[18F]fluoro‐L‐DOPA, used routinely in our Positron Emission Tomography program on neurodegenerative diseases as a tracer of the cerebral dopamine metabolism. The chemical pathway described for the total synthesis of our labelling precursor uses a straightforward protection sequence. This 4‐step chemical synthesis allows the rapid preparation of several grammes of pure material in good overall yield. Regioselective radiofluorodestannylation using [18F]fluorine ([18F]F2, cyclotron‐produced isotope, half‐life:110 min) gave pure 6‐[18F]fluoro‐L‐DOPA (8) in good radiochemical yield (26% decay‐corrected, based on starting [18F]fluorine recovered from the target) in 45–50 min after the End of Bombardment. The product was found to be >99% chemically, radiochemically and enantiomerically pure. © 1998 John Wiley & Sons, Ltd.