A copper-mediated radiofluorination of aryl- and vinylboronic acids with K18F is described. This method exhibits high functional group tolerance and is effective for the radiofluorination of a range ...of electron-deficient, -neutral, and -rich aryl-, heteroaryl-, and vinylboronic acids. This method has been applied to the synthesis of 18FFPEB, a PET radiotracer for quantifying metabotropic glutamate 5 receptors.
A practical, rapid, and highly regioselective Cu-catalyzed radiofluorination of (mesityl)(aryl)iodonium salts is described. This protocol utilizes 18FKF to access 18F-labeled electron-rich, ...-neutral, and -deficient aryl fluorides under a single set of mild conditions. This methodology is applied to the synthesis of protected versions of two important radiotracers: 4-18Ffluorophenylalanine and 6-18FfluoroDOPA.
The last 2-3 years have seen numerous relationships develop between organometallic chemists, fluorine chemists and PET Centers around the world. These collaborations have led to the development of ...many new strategies for the late-stage introduction of fluorine-18 into complex bioactive molecules. In this perspective we highlight recent developments and key milestones since 2011.
In this perspective we highlight recent developments and key milestones in "late-stage fluorination" since 2011.
A copper-mediated method for the transformation of diverse arylboron compounds and arylstannanes to aryl-
C-nitriles is reported. This method is operationally simple, uses commercially available ...reagents, and is compatible with a wide variety of substituted aryl- and heteroaryl substrates. This method is applied to the automated synthesis of high specific activity
Cperampanel in 10% nondecay-corrected radiochemical yield (RCY).
In a relatively short period of time, transition metal-mediated radiofluorination reactions have changed the PET radiochemistry landscape. These reactions have enabled the radiofluorination of a wide ...range of substrates, facilitating access to radiopharmaceuticals that were challenging to synthesize using traditional fluorine-18 radiochemistry. However, the process of adapting these new reactions for automated radiopharmaceutical production has revealed limitations in fitting them into the confines of traditional radiochemistry systems. In particular, the presence of bases (e.g. K
CO
) and/or phase transfer catalysts (PTC) (e.g. kryptofix 2.2.2) associated with fluorine-18 preparation has been found to be detrimental to reaction yields. We hypothesized that these limitations could be addressed through the development of alternate techniques for preparing
Ffluoride. This approach also opens the possibility that an eluent can be individually tailored to meet the specific needs of a metal-catalyzed reaction of interest. In this communication, we demonstrate that various solutions of copper salts, bases, and ancillary ligands can be utilized to elute
Ffluoride from ion exchange cartridges. The new procedures are effective for fluorine-18 radiochemistry and, as proof of concept, have been used to optimize an otherwise base-sensitive copper-mediated radiofluorination reaction.
A one-pot two-step synthesis of 6-
Ffluoro-l-DOPA (
FFDOPA) has been developed involving Cu-mediated radiofluorination of a pinacol boronate ester precursor. The method is fully automated, provides
...FFDOPA in good activity yield (104 ± 16 mCi, 6 ± 1%), excellent radiochemical purity (>99%) and high molar activity (3799 ± 2087 Ci mmol
), n = 3, and has been validated to produce the radiotracer for human use.
In this Viewpoint, we highlight the history of positron emission tomography (PET) radiotracer development to quantify changes in monoamine oxidase (MAO)-A and -B enzyme expression or activity. MAO-A ...and MAO-B are critical for understanding monoaminergic pathways in psychiatric addiction disorders, and more recently in neurodegenerative disorders with MAO-B expression in astrogliosis. Unique radiochemical innovations have been shown for neuroimaging of MAOs including the clinical translation of irreversible propargylamine-based suicide inhibitors, application of deuterium-substitution to slow down metabolism, development of trapped metabolite imaging agents, and unique
C-carbonylation chemistry toward novel high-affinity reversibly binding inhibitors.
This article describes a sequential Ir/Cu-mediated process for the
selective C-H radiofluorination of (hetero)arene substrates. In the first step, Ir-catalyzed C(sp
)-H borylation affords ...(hetero)aryl pinacolboronate (BPin) esters. The intermediate organoboronates are then directly subjected to copper-mediated radiofluorination with
Ftetrabutylammonium fluoride to afford fluorine-18 labeled (hetero)arenes in high radiochemical yield and radiochemical purity. This entire process is performed on a benchtop without Schlenk or glovebox techniques and circumvents the need to isolate (hetero)aryl boronate esters. The reaction was automated on a TracerLab FX
module with 1,3-dimethoxybenzene and a
tyrosine derivative. The products,
F1-fluoro-3,5-dimethoxybenzene and an
F-labeled
tyrosine derivative, were obtained in 37 ± 5% isolated radiochemical yield and >99% radiochemical purity and 25% isolated radiochemical yield and 99% radiochemical purity, and 0.52 Ci/μmol (19.24 GBq/μmol) molar activity (
), respectively.
ABSTRACT A new automated radiosynthesis of 11 C2‐(2,6‐difluoro‐4‐((2‐( N ‐methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ( 11 CK2), a radiopharmaceutical for the glutamate ...α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor, is reported. Although manual syntheses have been described, these are unsuitable for routine production of larger batches of 11 CK2 for (pre)clinical PET imaging applications. To meet demands for the imaging agent from our functional neuroimaging collaborators, herein, we report a current good manufacturing practice (cGMP)‐compliant synthesis of 11 CK2 using a commercial synthesis module. The new synthesis is fully automated and has been validated for clinical use. The total synthesis time is 33 min from end of bombardment, and the production method provides 2.66 ± 0.3 GBq (71.9 ± 8.6 mCi) of 11 CK2 in 97.7 ± 0.5% radiochemical purity and 754.1 ± 231.5 TBq/mmol (20,382.7 ± 6256.1 Ci/mmol) molar activity ( n = 3). Batches passed all requisite quality control testing confirming suitability for clinical use.
![Synthesis of [18F]Arenes vi...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1523-7060/small "Synthesis of [18F]Arenes via the Copper-Mediated [18F]Fluorination of Boronic Acids")
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![Late-stage [18F]fluorinatio...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/2041-6520_2041-6539/small "Late-stage [18F]fluorination: new solutions to old problems")
![Copper(II)-Mediated [ 11 C]...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1523-7052_1523-7060/small "Copper(II)-Mediated [ 11 C]Cyanation of Arylboronic Acids and Arylstannanes")
