Ring-Closing Synthesis of Dibenzothiophene Sulfonium Salts and Their Use as Leaving Groups for Aromatic <sup>18</sup>F-Fluorination

Gendron, Thibault; Sander, Kerstin; Cybulska, Klaudia; Benhamou, Laure; Sin, Pak Kwan Brian; Khan, Aqsa; Wood, Michael L.; Porter, Michael J.; Årstad, Erik

doi:10.1021/jacs.8b06730

Cited by 69 publications

(79 citation statements)

References 41 publications

(72 reference statements)

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“…36,37 As part of the neuroinflammatory response, astrogliosis has been widely studied in epilepsy, including PET studies in epileptic patients. 27 In vitro autoradiography with this tracer showed a late response of astrocytes compared to the TSPO up-regulation seen with 18 F-flutriciclamide. Here, we tested a novel PET tracer, 18 F-deprenyl, targeting MAO-B as a marker of astrocyte activation.…”

Section: Discussionmentioning

confidence: 88%

“…27 [ 18 F]FPEB was obtained in 55 ± 3 (n = 12) d.c. RCY with a radiochemical purity > 98% and a molar activity of 13-20 GBq/μmol. 27 [ 18 F]FPEB was obtained in 55 ± 3 (n = 12) d.c. RCY with a radiochemical purity > 98% and a molar activity of 13-20 GBq/μmol.…”

Section: Radiochemistrymentioning

confidence: 99%

“…The radiosyntheses of 18 F-FPEB and 3-18 F-fluorodeprenyl were carried out at the University College London as previously reported. 27 [ 18 F]FPEB was obtained in 55 ± 3 (n = 12) d.c. RCY with a radiochemical purity > 98% and a molar activity of 13-20 GBq/μmol. 3-18 F-fluorodeprenyl was obtained in 32 ± 2% (n = 3) d.c. RCY, the radiochemical purity was >98% and the molar activity of the tracer was 17-30 GBq/μmol.…”

Section: Radiochemistrymentioning

confidence: 99%

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Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers

et al. 2019

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Objective Identification of patients at risk of developing epilepsy before the first spontaneous seizure may promote the development of preventive treatment providing opportunity to stop or slow down the disease. Methods As development of novel radiotracers and on‐site setup of existing radiotracers is highly time‐consuming and expensive, we used dual‐centre in vitro autoradiography as an approach to characterize the potential of innovative radiotracers in the context of epilepsy development. Using brain slices from the same group of rats, we aimed to characterise the evolution of neuroinflammation and expression of inhibitory and excitatory neuroreceptors during epileptogenesis using translational positron emission tomography (PET) tracers; 18F‐flumazenil (18F‐FMZ; GABAA receptor), 18F‐FPEB (metabotropic glutamate receptor 5; mGluR5), 18F‐flutriciclamide (translocator protein; TSPO, microglia activation) and 18F‐deprenyl (monoamine oxidase B, astroglia activation). Autoradiography images from selected time points after pilocarpine‐induced status epilepticus (SE; baseline, 24 and 48 hours, 5, 10 and 15 days and 6 and 12‐14 weeks after SE) were normalized to a calibration curve, co‐registered to an MRI‐based 2D region‐of‐interest atlas, and activity concentration (Bq/mm2) was calculated. Results In epileptogenesis‐associated brain regions, 18F‐FMZ and 18F‐FPEB showed an early decrease after SE. 18F‐FMZ decrease was maintained in the latent phase and further reduced in the chronic epileptic animals, while 18F‐FPEB signal recovered from day 10, reaching baseline levels in chronic epilepsy. 18F‐flutriciclamide showed an increase of activated microglia at 24 hours after SE, peaking at 5‐15 days and decreasing during the chronic phase. On the other hand, 18F‐deprenyl autoradiography showed late astrogliosis, peaking in the chronic phase. Significance Autoradiography revealed different evolution of the selected targets during epileptogenesis. Our results suggest an advantage of combined imaging of inter‐related targets like glutamate and GABAA receptors, or microglia and astrocyte activation, in order to identify important interactions, especially when using PET imaging for the evaluation of novel treatments.

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Section: Discussionmentioning

confidence: 88%

Section: Radiochemistrymentioning

confidence: 99%

Section: Radiochemistrymentioning

confidence: 99%

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Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers

et al. 2019

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“…amines, fluorides) provides direct access to av ariety of important arylated compounds. [10] All thesea chievements have verified the great usefulnesso fa rylsulfonium salts in the carbon-carbon and carbonheteroatom bonds formation reactions. Despite the fact that transition-metal-free alkaline decomposition of triarylsulfonium salts gave diversep roducts via aromatic nucleophilic substitution, aryne intermediates,o rr adical processes, which were dependentupon the nature of bases and anionsofthe sulfonium salts, [11] the synthetic utility of these transformations was not recognized, possibly owing to the complicated product mix-tures generated from the reported reactions.…”

Section: Introductionmentioning

confidence: 79%

Base‐Mediated O‐Arylation of Alcohols and Phenols by Triarylsulfonium Triflates

Ming

Tian

Zhang

2019

Chemistry An Asian Journal

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A mild and efficient protocol for O‐arylation of alcohols and phenols (ROH) by triarylsulfonium triflates was developed under transition‐metal‐free conditions. Various alcohols, including primary, secondary and tertiary, and phenols bearing either electron‐donating or electron‐withdrawing groups on the aryl rings were smoothly converted to form the corresponding aromatic ethers in moderate to excellent yields. The reactions were conducted at 50 or 80 °C for 24 h in the presence of a certain base and showed good functional group tolerance. The base‐mediated arylation with asymmetric triarylsulfonium salts could selectively transfer the aryl groups of sulfoniums to ROH, depending on their inherent electronic nature. The mechanistic studies revealed that the reaction might proceed through the nucleophilic attack of the in situ formed alkoxy or phenoxy anions at the aromatic carbon atoms of the C−S bonds of triarylsulfonium cations to furnish the target products.

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“…Traditionally, high radiochemical yields (RCYs) and molar activities (A m s) can be achieved with nucleophilic labelling, but the reactivity scope is limited. Several methods have recently been introduced to improve nucleophilic 18 F‐labelling reactions; for example, the use of iodonium or sulfonium salts enables 18 F‐labelling of nonactivated aromatic compounds. Recently, a new pathway, termed transition metal–mediated 18 F‐fluorination, was introduced to produce 18 F‐labelled arenes with high A m s .…”

Section: Introductionmentioning

confidence: 99%

Radiosynthesis of the norepinephrine transporter tracer [¹⁸F]NS12137 via copper‐mediated ¹⁸F‐labelling

Lahdenpohja

Keller

Rajander

et al. 2019

Labelled Comp Radiopharmac

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[ 18 F]NS12137 ( exo ‐3‐[(6‐[ 18 F]fluoro‐2‐pyridyl)oxy]8‐azabicyclo[3.2.1]octane) is a highly selective norepinephrine transporter (NET) tracer. NETs are responsible for the reuptake of norepinephrine and dopamine and are linked to several neurodegenerative and neuropsychiatric disorders. The aim of this study was to develop a copper‐mediated 18 F‐fluorination method for the production of [ 18 F]NS12137 with straightforward synthesis conditions and high radiochemical yield and molar activity. [ 18 F]NS12137 was produced in two steps. Radiofluorination of [ 18 F]NS12137 was performed via a copper‐mediated pathway starting with a stannane precursor and using [ 18 F]F − as the source of the fluorine‐18 isotope. Deprotection was performed via acid hydrolysis. The radiofluorination reaction was nearly quantitative as was the deprotection based on HPLC analysis. The radiochemical yield of the synthesis was 15.1 ± 0.5%. Molar activity of [ 18 F]NS12137 was up to 300 GBq/μmol. The synthesis procedure is straightforward and can easily be automated and adapted for clinical production.

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Ring-Closing Synthesis of Dibenzothiophene Sulfonium Salts and Their Use as Leaving Groups for Aromatic ¹⁸F-Fluorination

Cited by 69 publications

References 41 publications

Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers

Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers

Base‐Mediated O‐Arylation of Alcohols and Phenols by Triarylsulfonium Triflates

Radiosynthesis of the norepinephrine transporter tracer [¹⁸F]NS12137 via copper‐mediated ¹⁸F‐labelling

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Ring-Closing Synthesis of Dibenzothiophene Sulfonium Salts and Their Use as Leaving Groups for Aromatic 18F-Fluorination

Cited by 69 publications

References 41 publications

Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers

Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers

Base‐Mediated O‐Arylation of Alcohols and Phenols by Triarylsulfonium Triflates

Radiosynthesis of the norepinephrine transporter tracer [18F]NS12137 via copper‐mediated 18F‐labelling

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Resources

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Ring-Closing Synthesis of Dibenzothiophene Sulfonium Salts and Their Use as Leaving Groups for Aromatic ¹⁸F-Fluorination

Radiosynthesis of the norepinephrine transporter tracer [¹⁸F]NS12137 via copper‐mediated ¹⁸F‐labelling