No-Carrier-Added [18F]Fluorobenzene Derivatives as Intermediates for Built-up Radiosyntheses

Labelled Comp Radiopharmac

Coenen

2013

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The D(4) receptor is of high interest for research and clinical application but puts high demands on appropriate radioligands to be useful tools for investigation. Search for adequate radioligands suitable for in vivo imaging is therefore still in progress. The potential neuroleptic drug 6-(4-[4-fluorobenzyl]piperazin-1-yl)benzodioxin shows high affinity and selectivity to the D(4) receptor. Derivatization of this lead structure by adding hydrophilic moieties was carried out in order to lower its lipophilicity what led to three new putative dopamine receptor D(4) ligands. A comprehensive description of the syntheses of standard compounds and corresponding labeling precursors is given which were obtained in satisfactory yields. Furthermore, the radiosyntheses by direct (18) F-labeling and build-up synthesis were compared. All derivatives of 6-(4-[4-fluorobenzyl]-piperazin-1-yl)benzodioxin were successfully synthesized in (18) F-labeled form with radiochemical yields of 9-35% and molar activities of 30-60 GBq/µmol using one-pot procedures.

Section: Comparison Of Methodsmentioning

confidence: 99%

Labeling of benzodioxin piperazines with fluorine‐18 as prospective radioligands for selective imaging of dopamine D₄ receptors

Kügler

Labelled Comp Radiopharmac

Coenen

2013

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“…the influence of oxidant, acid, and solvent on the formation and rearrangement of the Criegee intermediates . The usefulness of alternative oxidation reagents like the hypervalent aryl‐λ‐bromane, on the other hand, is severely limited, since the synthesis of this reagent is hardly amenable, although it provides a very potent BVO method towards the chemoselective formation of phenols …”

Section: Resultsmentioning

confidence: 99%

“…The [ 18 F]fluorophenol moiety is part of a variety of established and potential radiopharmaceuticals, like several aromatic amino acids, biogenic aromatic amines, and receptor ligands . To obtain [ 18 F]‐fluorophenol derivatives of high molar activity, its n.c.a.…”

Section: Introductionmentioning

confidence: 99%

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

Labelled Comp Radiopharmac

Meleán

Humpert

et al. 2019

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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.

“…The iodonium strategy (method ii), which was for the first time introduced into 18 Fradiochemistry in 1995 [108,138,139], and the use of triarylsulfonium salts [140] were initially limited to the synthesis of small molecules, like 1-bromo-4-[ 18 F]fluorobenzene [141] and 1-[ 18 F]fluoro-4-iodobenzene [142,143]. The latter served especially as building blocks in transition metal-mediated reactions for the synthesis of 18 F-radiotracers [128,144]. This type of reaction has been well established in commercially available synthesis devices [145].…”

Section: Progress In Aromatic Nucleophilic 18 F-fluorinationmentioning

confidence: 99%

18F-labelling innovations and their potential for clinical application

Coenen

2018

Clin Transl Imaging

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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.