Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of ¹⁸F-difluoromethylarenes using aryl boronic acids, ethyl bromofluoroacetate and [¹⁸F]fluoride.

ABSTRACT: Herein, we report the radiosynthesis of ¹⁸F-difluoromethylarenes via the assembly of three components, a boron reagent, ethyl bromofluoroacetate, and cyclotron-produced non-carrier added [¹⁸F]fluoride. The two key steps are a copper-catalysed cross-coupling reaction, and a Mn-mediated ¹⁸F-fluorodecarboxylation.

SUBMITTER: Sap JBI

PROVIDER: S-EPMC6429591 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis of 18F-difluoromethylarenes using aryl boronic acids, ethyl bromofluoroacetate and [18F]fluoride.

Sap Jeroen B I JBI Wilson Thomas C TC Kee Choon Wee CW Straathof Natan J W NJW Ende Christopher W Am CWA Mukherjee Paramita P Zhang Lei L Genicot Christophe C Gouverneur Véronique V

Chemical science 20190129 11

Herein, we report the radiosynthesis of 18F-difluoromethylarenes via the assembly of three components, a boron reagent, ethyl bromofluoroacetate, and cyclotron-produced non-carrier added [18F]fluoride. The two key steps are a copper-catalysed cross-coupling reaction, and a Mn-mediated 18F-fluorodecarboxylation. ...[more]

PMID: 30996907

Similar Datasets

Fast and efficient copper-mediated 18F-fluorination of arylstannanes, aryl boronic acids, and aryl boronic esters without azeotropic drying.

Project description:BackgroundCopper-mediated radiofluorination is a straightforward method to produce a variety of [18F]fluoroarenes and [18F]fluoroheteroarenes. To minimize the number of steps in the production of 18F-labelled radiopharmaceuticals, we have developed a short and efficient azeotropic drying-free 18F-labelling method using copper-mediated fluorination. Our goal was to improve the copper-mediated method to achieve wide substrate scope with good radiochemical yields with short synthesis time.ResultsSolid phase extraction with Cu (OTf)2 in dimethylacetamide is a suitable activation method for [18F]fluoride. Elution efficiency with Cu (OTf)2 is up to 79% and radiochemical yield (RCY) of a variety of model molecules in the crude reaction mixture has reached over 90%. Clinically relevant molecules, norepinephrine transporter tracer [18F]NS12137 and monoamine transporter tracer [18F]CFT were produced with 16.5% RCY in 98?min and 5.3% RCY in 64?min, respectively.ConclusionsCu (OTf)2 is a suitable elution agent for releasing [18F]fluoride from an anion exchange cartridge. The method is fast and efficient and the Cu-complex is customizable after the release of [18F]fluoride. Alterations in the [18F]fluoride elution techniques did not have a negative effect on the subsequent labelling reactions. We anticipate this improved [18F]fluoride elution technique to supplant the traditional azeotropic drying of [18F]fluoride in the long run and to concurrently enable the variations of the copper-complex.

| S-EPMC6795642 | biostudies-literature

Synthesis and evaluation of aryl boronic acids as fluorescent artificial receptors for biological carbohydrates.

Project description:Carbohydrates in various forms play a vital role in numerous critical biological processes. The detection of such saccharides can give insight into the progression of such diseases such as cancer. Boronic acids react with 1,2 and 1,3 diols of saccharides in non-aqueous or basic aqueous media. Herein, we describe the design, synthesis and evaluation of three bisboronic acid fluorescent probes, each having about ten linear steps in its synthesis. Among these compounds that were evaluated, 9b was shown to selectively label HepG2, liver carcinoma cell line within a concentration range of 0.5-10 ?M in comparison to COS-7, a normal fibroblast cell line.

| S-EPMC3306810 | biostudies-literature

[18F]Tosyl fluoride as a versatile [18F]fluoride source for the preparation of 18F-labeled radiopharmaceuticals.

Project description:Positron emission tomography (PET) is an in vivo imaging technology that utilizes positron-emitting radioisotope-labeled compounds as PET radiotracers that are commonly used in clinic and in various research areas, including oncology, cardiology, and neurology. Fluorine-18 is the most widely used PET-radionuclide and commonly produced by proton bombardment of 18O-enriched water in a cyclotron. The [18F]fluoride thus obtained generally requires processing by azeotropic drying in order to completely remove H2O before it can be used for nucleophilic radiofluorination. In general, the drying step is important in facilitating the radiofluorination reactions and the preparation of 18F-labeled PET radiotracers. In this communication, we have demonstrated the feasibility of using [18F]tosyl fluoride ([18F]TsF) as a versatile [18F]fluoride source for radiofluorination to bypass the azeotropic drying step, and we have developed a continuous flow solid-phase radiosynthesis strategy to generate [18F]TsF in a form that is excellent for radiofluorination. [18F]TsF shows high reactivity in radiofluorination and provides the features suitable for preparing PET radiotracers on a small scale and exploring novel radiolabeling technologies. Thus, using [18F]TsF as a [18F]fluoride source is a promising strategy that facilitates radiofluorination and provides a convenient and efficient solution for the preparation of 18F-labeled radiopharmaceuticals that is well matched to the emerging trends in PET imaging technologies.

| S-EPMC9950486 | biostudies-literature

Palladium-Catalyzed 1,3-Difunctionalization Using Terminal Alkenes with Alkenyl Nonaflates and Aryl Boronic Acids.

Project description:A Pd-catalyzed 1,3-difunctionalization of terminal alkenes using 1,1-disubstituted alkenyl nonaflates and arylboronic acid coupling partners is reported. This transformation affords allylic arene products that are difficult to selectively access using traditional Heck cross-coupling methodologies. The evaluation of seldom employed 1,1-disubstituted alkenyl nonaflate coupling partners led to the elucidation of subtle mechanistic features of π-allyl stabilized Pd-intermediates. Good stereo- and regioselectivity for the formation of 1,3-addition products can be accessed through a minimization of steric interactions that emanate from alkenyl nonaflate substitution.

| S-EPMC5053098 | biostudies-literature

[18F]fluoride Activation and 18F-Labelling in Hydrous Conditions-Towards a Microfluidic Synthesis of PET Radiopharmaceuticals.

Project description:18F-labelled radiopharmaceuticals are indispensable in positron emission tomography. The critical step in the preparation of 18F-labelled tracers is the anhydrous F-18 nucleophilic substitution reaction, which involves [18F]F- anions generated in aqueous media by the cyclotron. For this, azeotropic drying by distillation is widely used in standard synthesisers, but microfluidic systems are often not compatible with such a process. To avoid this step, several methods compatible with aqueous media have been developed. We summarised the existing approaches and two of them have been studied in detail. [18F]fluoride elution efficiencies have been investigated under different conditions showing high 18F-recovery. Finally, a large scope of precursors has been assessed for radiochemical conversion, and these hydrous labelling techniques have shown their potential for tracer production using a microfluidic approach, more particularly compatible with iMiDEV™ cassette volumes.

| S-EPMC10779751 | biostudies-literature

Palladium-Catalyzed Defluorinative Coupling of 1-Aryl-2,2-Difluoroalkenes and Boronic Acids: Stereoselective Synthesis of Monofluorostilbenes.

Project description:The palladium-catalyzed defluorinative coupling of 1-aryl-2,2-difluoroalkenes with boronic acids is described. Broad functional-group tolerance arises from a redox-neutral process by a palladium(II) active species which is proposed to undergo a β-fluoride elimination to afford the products. The monofluorostilbene products were formed with excellent diastereoselectivity (≥50:1) in all cases, and it is critical, as traditional chromatographic techniques often fail to separate monofluoroalkene isomers. As a demonstration of this method's unique combination of reactivity and functional-group tolerance, a Gleevec® analogue, using a monofluorostilbene as an amide isostere, was synthesized.

| S-EPMC5176253 | biostudies-literature

A Transmetalation Reaction Enables the Synthesis of [18F]5-Fluorouracil from [18F]Fluoride for Human PET Imaging.

Project description:Translation of new 18F-fluorination reactions to produce radiotracers for human positron emission tomography (PET) imaging is rare because the chemistry must have useful scope and the process for 18F-labeled tracer production must be robust and simple to execute. The application of transition metal mediators has enabled impactful 18F-fluorination methods, but to date none of these reactions have been applied to produce a human-injectable PET tracer. In this article we present chemistry and process innovations that culminate in the first production from [18F]fluoride of human doses of [18F]5-fluorouracil, a PET tracer for cancer imaging in humans. The first preparation of nickel σ-aryl complexes by transmetalation from arylboronic acids or esters was developed and enabled the synthesis of the [18F]5-fluorouracil precursor. Routine production of >10 mCi doses of [18F]5-fluorouracil was accomplished with a new instrument for azeotrope-free [18F]fluoride concentration in a process that leverages the tolerance of water in nickel-mediated 18F-fluorination.

| S-EPMC4829938 | biostudies-literature

Chiral Aniline Synthesis via Stereospecific C(sp3)-C(sp2) Coupling of Boronic Esters with Aryl Hydrazines.

Project description:An enantiospecific coupling between alkylboronic esters and lithiated aryl hydrazines is described. The reaction proceeds under transition-metal-free conditions and is promoted by acylation of a hydrazinyl arylboronate complex, which triggers a N-N bond cleavage with concomitant 1,2-metalate rearrangement. Judicious choice of the acylating agent enabled the synthesis of ortho- and para-substituted anilines with essentially complete enantiospecificity from a wide range of boronic ester substrates.

| S-EPMC6178205 | biostudies-literature

Synthesis of aryldifluoromethyl aryl ethers via nickel-catalyzed suzuki cross-coupling between aryloxydifluoromethyl bromides and boronic acids.

Project description:As a unique organofluorine fragment, gem-difluoromethylated motifs have received widespread attention. Here, a convenient and efficient synthesis of aryldifluoromethyl aryl ethers (ArCF2OAr') was established via Nickel-catalyzed aryloxydifluoromethylation with arylboronic acids. This approach features easily accessible starting materials, good tolerance of functionalities, and mild reaction conditions. Diverse late-stage difluoromethylation of many pharmaceuticals and natural products were readily realized. Notably, a new difluoromethylated PD-1/PD-L1 immune checkpoint inhibitor was conveniently synthesized and showed both improved metabolic stability and enhanced antitumor efficacy. Preliminary mechanistic studies suggested the involvement of a Ni(I/III) catalytic cycle.

| S-EPMC9814959 | biostudies-literature

A Practical Method for the Preparation of 18F-Labeled Aromatic Amino Acids from Nucleophilic [18F]Fluoride and Stannyl Precursors for Electrophilic Radiohalogenation.

Project description:In a recent contribution of Scott et al., the substrate scope of Cu-mediated nucleophilic radiofluorination with [18F]KF for the preparation of 18F-labeled arenes was extended to aryl- and vinylstannanes. Based on these findings, the potential of this reaction for the production of clinically relevant positron emission tomography (PET) tracers was investigated. To this end, Cu-mediated radiofluorodestannylation using trimethyl(phenyl)tin as a model substrate was re-evaluated with respect to different reaction parameters. The resulting labeling protocol was applied for 18F-fluorination of different electron-rich, -neutral and -poor arylstannyl substrates in RCCs of 16-88%. Furthermore, this method was utilized for the synthesis of 18F-labeled aromatic amino acids from additionally N-Boc protected commercially available stannyl precursors routinely applied for electrophilic radiohalogenation. Finally, an automated synthesis of 6-[18F]fluoro-l-m-tyrosine (6-[18F]FMT), 2-[18F]fluoro-l-tyrosine (2-[18F]F-Tyr), 6-[18F]fluoro-l-3,4-dihydroxyphenylalanine (6-[18F]FDOPA) and 3-O-methyl-6-[18F]FDOPA ([18F]OMFD) was established furnishing these PET probes in isolated radiochemical yields (RCYs) of 32-54% on a preparative scale. Remarkably, the automated radiosynthesis of 6-[18F]FDOPA afforded an exceptionally high RCY of 54 ± 5% (n = 5).

| S-EPMC6149761 | biostudies-literature