Stereoselective radiosynthesis of l- and d-3-[18F]fluoro-α-methyltyrosine

Labelled Comp Radiopharmac

Meleán

Humpert

et al. 2019

Self Cite

A reaction pathway via oxidation of [ 18 F]fluorobenzaldehydes offers a very useful tool for the no-carrier-added radiosynthesis of [ 18 F]fluorophenols, a structural motive of several potential radiopharmaceuticals. A considerably improved chemoselectivity of the Baeyer-Villiger oxidation (BVO) towards phenols was achieved, employing 2,2,2-trifluoroethanol as reaction solvent in combination with Oxone or m-CPBA as oxidation agent. The studies showed the necessity of H 2 SO 4 addition, which appears to have a dual effect, acting as catalyst and desiccant. For example, 2-[ 18 F]fluorophenol was obtained with a RCY of 97% under optimised conditions of 80°C and 30-minute reaction time.The changed performance of the BVO, which is in agreement with known reaction mechanisms via Criegee intermediates, provided the best results with regard to radiochemical yield (RCY) and chemoselectivity, i.e. formation of [ 18 F]fluorophenols rather than [ 18 F]fluorobenzoic acids. Thus, after a long history of the BVO, the new modification now allows an almost specific formation of phenols, even from electron-deficient benzaldehydes. Further, the applicability of the tuned, chemoselective BVO to the n.c.a. level and to more complex compounds was demonstrated for the products n.c.a. 4-[ 18 F]fluorophenol (RCY 95%; relating to 4-[ 18 F]fluorobenzaldehyde) and 4-[ 18 F]fluoro-m-tyramine (RCY 32%; relating to [ 18 F]fluoride), respectively.

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Baeyer‐Villiger oxidation tuned to chemoselective conversion of non‐activated [¹⁸F]fluorobenzaldehydes to [¹⁸F]fluorophenols

Labelled Comp Radiopharmac

Meleán

Humpert

et al. 2019

Self Cite

“…An alternative carbonyl-activated, three-step 18 F-fluorination was realized for the syntheses of the aromatic 18 F-labelled amino acids 6-[ 18 [134] and L-and D-3-[ 18 F]fluoro-α-methyltyrosine [135] (see Fig. 3).…”

Section: Progress In Aromatic Nucleophilic 18 F-fluorinationmentioning

confidence: 99%

18F-labelling innovations and their potential for clinical application

Coenen

2018

Clin Transl Imaging

Self Cite

An impressive variety of new methodologies for the preparation of 18 F-labelled tracers and ligands has appeared over the last decade. Most strategies of the newly developed radiofluorination methods predominantly aim at products of high molar activity by 'late-stage' labelling of small (hetero)aromatic molecules and the use of transition metals. This is accompanied by the improvement of technical procedures, like preparation of reactive [ 18 F]fluoride and automated syntheses. The newly introduced procedures reflect a high innovative level and creativity in radio(pharmaceutical) chemistry at present, which are based on modern chemical methods and deep mechanistic insights. Taking also automation and quality control into consideration, major recently developed radiofluorination methods, most of those still under development, are compiled here in view of their potential for clinical PET imaging and thus the ability to advance molecular imaging.

“…The use of the Baeyer–Villiger oxidation for the formation of 18 F‐labeled aromatic amino acids was primarily suggested by Chakraborty and Kilbourn, but its realization was not published . A first attempt to synthesize 6‐[ 18 F]FDOPA by this method was described by Tierling et al In the meantime, this procedure was improved and transferred to the synthesis of 6‐[ 18 F]FDOPA, 3‐[ 18 F]fluoro‐α‐methyltyrosine ([ 18 F]FAMT), 2‐[ 18 F]fluorophenylalanine ([ 18 F]Fphe), and 2‐[ 18 F]fluorotyrosine (2‐[ 18 F]Ftyr) . The isotopic exchange enabled an S N Ar reaction under relatively mild conditions because of the good leaving ability of fluoride.…”

Section: Introductionmentioning

confidence: 99%

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

Meleán

Labelled Comp Radiopharmac

Coenen

2015

Self Cite

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%.