A three-step radiosynthesis of 6-[18 F]fluoro-L-meta-tyrosine starting with [18 F]fluoride

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 58; no. 3; pp. 133 - 140
• Main Authors: Castillo Meleán, Johnny, Ermert, Johannes, Coenen, Heinz H.
• Format: Journal Article
• Language: English; French; German
• Published: HOBOKEN Blackwell Publishing Ltd 01.03.2015; Wiley; Wiley Subscription Services, Inc
• Subjects: 6-[18 F]fluoro-L-m-tyrosine; Baeyer-Villiger oxidation; Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry; Chemistry Techniques, Synthetic; Chemistry, Analytical; Chemistry, Medicinal; Fluorides; Fluorides - chemistry; Fluorine Radioisotopes - chemistry; fluorine-18; Halogenation; Hydrolysis; Isotopes; isotopic exchange; Life Sciences & Biomedicine; Oxidation-Reduction; Pharmacology & Pharmacy; Physical Sciences; positron emission tomography; Radiochemistry; Science & Technology; Tyrosine - analogs & derivatives; Tyrosine - chemical synthesis; Tyrosine - chemistry; Baeyer-Villiger oxidation; OXIDATION; isotopic exchange; fluorine-18; 6-[F-18]fluoro-L-m-tyrosine; DIIODOSILANE; ANALOGS; AMINO-ACIDS; M-TYROSINE; KINETICS; DOPAMINE; positron emission tomography; 6-[18 F]fluoro-L-m-tyrosine
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.3273

The radiosynthesis of 6‐[18 F]fluoro‐L‐m‐tyrosine has generally been performed by electrophilic radiofluorination, which exhibits several drawbacks. In the present work, a three‐step radiochemical synthesis is described starting from [18 F]fluoride. The synthetic sequence, including isotopic exchange, Baeyer–Villiger oxidation, and hydrolysis, were examined comparing four fluorobenzophenone derivatives as labeling precursors. Of those, (2S,5S)‐tert‐butyl 5‐(5‐acetyl‐2‐fluorobenzyl)‐2‐tert‐butyl‐3‐methyl‐4‐oxoimidazolidine‐1‐carboxylate (1a) and (2S,5S)‐tert‐butyl 2‐tert‐butyl‐5‐(2‐fluoro‐5‐(2,2,2‐trifluoroacetyl)benzyl)‐3‐methyl‐4‐oxoimidazolidine‐1‐carboxylate (1d) proved to be the most suitable ones. 6‐[18 F]Fluoro‐L‐m‐tyrosine was obtained with overall radiochemical yields of 8–13% and an enantiomeric excess of up to 98%. The radiosynthesis of 6‐[18 F]fluoro‐L‐m‐tyrosine has generally been performed by electrophilic radiofluorination, which exhibits several drawbacks. In the present work, a three‐step radiochemical synthesis is described starting from [18F]fluoride. The synthetic sequence, including isotopic exchange, Baeyer‐Villiger oxidation, and hydrolysis, were examined comparing four fluorobenzophenone derivatives as labeling precursors. [18F]fluoro‐L‐m‐tyrosine was obtained with overall radiochemical yields of 8–13% and an enantiomeric excess of up to 98%.