Direct Nucleophilic 18F-Fluorination of Electron Rich Arenes: Present Limits of No-Carrier-Added Reactions

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A recently published palladium‐catalyzed preparation of fluoroarenes starting from caesium fluoride attracted interest as a new alternative for radiofluorination. To test this method, a suitable protocol for the synthesis of 4‐[18F]fluorotoluene and 1‐[18F]fluoronaphthalene as model systems has been developed. The possibility to perform the reaction under no‐carrier‐added condition was of special interest. It was found out, however, that the reaction requires the presence of carrier, thus limiting the method to syntheses of radiotracers with low specific activity. Copyright © 2012 John Wiley & Sons, Ltd.

Section: Resultsmentioning

confidence: 99%

“…fluorine‐18 into organic molecules by direct nucleophilic substitution or by several indirect routes, including even multistep syntheses, there is still a demand of efficient methods for the direct n.c.a. radiofluorination of electron‐rich arenes …”

Section: Introductionmentioning

confidence: 99%

Carrier‐effect on palladium‐catalyzed, nucleophilic ¹⁸F‐fluorination of aryl triflates

Cardinale

Neumaier

Kügler

et al. 2012

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“…The synthesis of 2‐(2‐[ 18 F]fluoro‐4‐nitrobenzamido)‐3‐methylbutanoic acid is an example of an acylation reaction. This derivative of the amino acid valine was 18 F‐labelled in a two‐step reaction, using a substituted benzoic acid for acylation that is highly activated for a nucleophilic aromatic substitution reaction …”

Section: F‐labelled Amino Acidsmentioning

confidence: 99%

Methods for ¹¹C‐ and ¹⁸F‐labelling of amino acids and derivatives for positron emission tomography imaging

Neumaier

Coenen

2013

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The different concepts realized for the synthesis of (11) C- and (18) F-labelled amino acids are summarized. Carbon-11 enables principally authentic radiolabelling of natural occurring amino acids by substituting one of the skeleton carbons by the radionuclide. Fluorine-18 is a foreign element for natural amino acids. Because of its advantageous nuclidic properties for positron emission tomography, however, it becomes increasingly important in molecular imaging, also with amino acid analogues. Especially in the last decade, considerable progress has been made with the radiosynthesis of (18) F-labelled amino acids that are now clinically approved, and thus assure their availability. In contrast, the synthetic possibilities with (11) C-labelled amino acids are more limited because of the short half-life of carbon-11 which also hampers their wide spread use.

“…These nucleophilic reactions usually involve no‐carrier‐added (high‐SRA) [ 18 F]fluoride, often as its K[ 18 F]F‐K222 complex and include especially S N 2‐type substitutions in the aliphatic series but also S N Ar‐type substitutions in the homo aromatic series . More recent advances include the use of iodonium salts as precursors for labelling, allowing fluorination of electron‐rich arenes (by homo aromatic nucleophilic substitutions with [ 18 F]fluoride), as well as nucleophilic hetero aromatic substitutions …”

Section: Introductionmentioning

confidence: 99%

The potential of carbon‐11 and fluorine‐18 chemistry: illustration through the development of positron emission tomography radioligands targeting the translocator protein 18 kDa

Damont

Roeda

Dollé

2013

The TSPO (translocator protein), also known as the peripheral benzodiazepine receptor, is upregulated in the brain of subjects suffering from neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease. Moreover, this overexpression has been proved to be linked to microglia activation making thus the TSPO a marker of choice of neuroinflammatory processes and therefore a potential target for the development of radioligands for positron emission tomography imaging. The discovery of selective TSPO ligands and their labelling with the short-lived positron-emitter isotopes carbon-11 and fluorine-18 emerged in the mid-1980s with the preparation of the 3-isoquinolinecarboxamide [(11) C]PK11195. To date, an impressive number of promising compounds-[(11) C]PK11195-challengers-have been developed; some radioligands-for example, [(11) C]PBR28, [(11) C]DPA-713, [(18) F]FEDAA1106 and [(18) F]DPA-714-are currently used in clinical trials. As illustrated in this review, the methodologies applied for the preparation of these compounds remain mainly [(11) C]methylations using [(11) C]MeI or [(11) C]MeOTf and SN 2-type nucleophilic aliphatic [(18) F]fluorinations-two processes illustrating the state-of-the-art arsenal of reactions that involves these two short-lived radioisotopes-but alternative processes, such as [(11) C]carbonylations using [(11) C]CO and [(11) C]COCl2 as well as SN Ar-type nucleophilic [(18) F]fluorinations, have also been reported and as such, reviewed herein.