Véronique Gouverneur

Véronique Gouverneur
University of Oxford | OX · Department of Chemistry

About

343
Publications
19,361
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17,513
Citations
Citations since 2016
76 Research Items
10270 Citations
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201620172018201920202021202205001,0001,500
201620172018201920202021202205001,0001,500

Publications

Publications (343)
Preprint
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Introduction: Radioligand therapy (RLT) is an expanding field that has shown great potential in the fight against cancer. Radionuclides that can be carried by selective ligands such as antibodies, peptides, and small molecules targeting cancerous cells have demonstrated a clear improvement in the move towards precision medicine. Poly (ADP-ribose) p...
Article
Full-text available
Purpose Radiopharmaceuticals targeting poly(ADP-ribose) polymerase (PARP) have emerged as promising agents for cancer diagnosis and therapy. PARP enzymes are expressed in both cancerous and normal tissue. Hence, the injected mass, molar activity and potential pharmacological effects are important considerations for the use of radiolabelled PARP inh...
Article
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Purpose Rucaparib, an FDA-approved PARP inhibitor, is used as a single agent in maintenance therapy to provide promising treatment efficacy with an acceptable safety profile in various types of BRCA -mutated cancers. However, not all patients receive the same benefit from rucaparib-maintenance therapy. A predictive biomarker to help with patient se...
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Purpose Ataxia telangiectasia mutated (ATM) is a key mediator of the DNA damage response, and several ATM inhibitors (ATMi) are currently undergoing early phase clinical trials for the treatment of cancer. A radiolabelled ATMi to determine drug pharmacokinetics could assist patient selection in a move towards more personalised medicine. The aim of...
Article
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The advent of total-body Positron Emission Tomography (PET) has vastly broadened the range of research and clinical applications of this powerful molecular imaging technology1. Such possibilities have accelerated progress in 18F-radiochemistry with numerous methods available to 18F-label (hetero)arenes and alkanes2. However, access to 18F-difluorom...
Article
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Background Flumazenil (FMZ) is a functionally silent imidazobenzodiazepine which binds to the benzodiazepine binding site of approximately 75% of the brain γ-aminobutyric acid-A receptors (GABAARs). Positron Emission Tomography (PET) imaging of the GABAARs with [¹¹C]FMZ has been used to evidence alterations in neuronal density, to assess target eng...
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Asymmetric catalytic azidation has increased in importance to access enantioenriched nitrogen containing molecules, but methods that employ inexpensive sodium azide remain scarce. This encouraged us to undertake a detailed study on the application of hydrogen bonding phase-transfer catalysis (HB-PTC) to enantioselective azidation with sodium azide....
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Boron is absent in proteins, yet is a micronutrient. It possesses unique bonding that could expand biological function including modes of Lewis acidity not available to typical elements of life. Here we show that post-translational Cβ–Bγ bond formation provides mild, direct, site-selective access to the minimally sized residue boronoalanine (Bal) i...
Article
Fluorine is a key element present in ~35% of agrochemicals and 25% of marketed pharmaceutical drugs. The availability of reliable synthetic protocols to prepare catalysts that allow the efficient incorporation of fluorine in organic molecules is therefore essential for broad applicability. Herein, we report a protocol for the multigram synthesis of...
Preprint
Full-text available
Purpose Radiopharmaceuticals targeting poly(ADP-ribose) polymerase (PARP) have emerged as promising agents for cancer diagnosis and therapy. PARP enzymes are expressed in both cancerous and normal tissue. Hence, the injected mass, molar activity and potential pharmacological effects are important considerations for the use of radiolabelled PARP inh...
Article
Full-text available
Positron emission tomography (PET) has become an invaluable tool for drug discovery and diagnosis. The positron-emitting radionuclide fluorine-18 is frequently used in PET radiopharmaceuticals due to its advantageous characteristics; hence, methods streamlining access to ¹⁸ F-labelled radiotracers can make a direct impact in medicine. For many year...
Article
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A process for the direct hydrofluoromethylation of alkenes is reported for the first time. This straighforward silyl radical-mediated reaction utilises CH2FI as a non-ozone depleting reagent, traditionally used in electrophilic, nucleophilic and carbene-type chemistry, but not as a CH2F radical source. By circumventing the challenges associated wit...
Article
Fluorinated molecules have a wide range of applications and are used as medicines, agrochemicals and refrigerants and in smartphone liquid crystal displays, photovoltaic solar cells, Teflon tapes and the coatings of textiles and buildings. Fluorination and fluoroalkylation — incorporation of a trifluoromethyl, difluoromethyl or monofluoromethyl gro...
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This review describes the recent advances made in difluoromethylation processes based on X-CF2H bond formation where X is C(sp), C(sp2), C(sp3), O, N or S, a field of research that has benefited from the invention of multiple difluoromethylation reagents. The last decade has witnessed an upsurge of metal-based methods that can transfer CF2H to C(sp...
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The carbonyl group is now a widely useful, nonproteinogenic functional group in chemical biology, yet methods for its generation in proteins have relied upon either cotranslational incorporation of unnatural amino acids bearing carbonyls or oxidative conversion (chemical or enzymatic) of existing natural amino acids. If available, alternative strat...
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Targeted radiotherapy with ¹³¹I-mIBG, a substrate of the human norepinephrine transporter (NET-1), shows promising responses in heavily pre-treated neuroblastoma (NB) patients. Combinatorial approaches that enhance ¹³¹I-mIBG tumour uptake are of substantial clinical interest but biomarkers of response are needed. Here, we investigate the potential...
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Hydrogen-bonding interactions have been explored in catalysis, enabling complex chemical reactions. Recently, enantioselective nucleophilic fluorination with metal alkali fluoride has been accomplished with BINAM-derived bisurea catalysts, presenting up to four NH hydrogen-bond donors (HBDs) for fluoride. These catalysts bring insoluble CsF and KF...
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Post-translational modifications (PTMs) greatly expand the structures and functions of proteins in nature1,2. Although synthetic protein functionalization strategies allow mimicry of PTMs3,4, as well as formation of unnatural protein variants with diverse potential functions, including drug carrying⁵, tracking, imaging⁶ and partner crosslinking⁷, t...
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Herein, we report a highly effective protocol for the cross-coupling of (hetero)aryl bromides with fluorinated alcohols using the commercially available precatalyst tBuBrettPhos Pd G3 and Cs2CO3 in toluene. This Pd-catalyzed coupling features a short reaction time, excellent functional group tolerance, and compatibility with electron-rich and -poor...
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Ammonium salts are used as phase-transfer catalysts for fluorination with alkali metal fluoride. We now demonstrate that these organic salts, specifically azetidinium triflates, are suitable substrates for enantioselective ring opening with CsF and a chiral bis-urea catalyst. This process that highlights the ability of hydrogen bonding phase-transf...
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Molecular editing such as insertion, deletion and single atom exchange in highly functionalized compounds is an aspira-tional goal for all chemists. Here, we disclose a photoredox protocol for the replacement of a single fluorine atom with hydrogen in a range of electron-deficient trifluoromethylarenes including complex drug molecules. A robustness...
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Background Poly (ADP-ribose) polymerase (PARP) inhibitors are extensively studied and used as anti-cancer drugs, as single agents or in combination with other therapies. Most radiotracers developed to date have been chosen on the basis of strong PARP1–3 affinity. Herein, we propose to study AZD2461, a PARP inhibitor with lower affinity towards PARP...
Article
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Radical new approach : Sulfonyl chlorides have been applied in the radical hydrosulfonylation of alkenes. Tris(trimethylsilyl)silane is an ideal hydrogen atom donor enabling highly effective photoredox‐catalyzed hydrosulfonylation of electron‐deficient alkenes with sulfonyl chlorides. To increase the generality of this transformation, polarity‐reve...
Article
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Sulfonyl chlorides are inexpensive reactants extensively explored for functionalization, but never considered for radical hydrosulfonylation of alkenes. Herein, we report that tris(trimethylsilyl)silane is an ideal hydrogen atom donor enabling highly effective photoredox‐catalyzed hydrosulfonylation of electron‐deficient alkenes with sulfonyl chlor...
Article
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Positron emission tomography (PET) is a diagnostic nuclear imaging modality that relies on automated protocols to prepare agents labeled with a positron-emitting radionuclide (e.g., ¹⁸F). In recent years, new reactions have appeared for the ¹⁸F-labeling of agents that are difficult to access by applying traditional radiochemistry, for example those...
Article
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18F-Labeling strategies for unmodified peptides with [18F]fluoride require 18F-prosthetics for bioconjugation more often with cysteine thiols or lysine amines. Here, we explore selective radical chemistry to target aromatic residues applying C–H 18F-trifluoromethylation. We report a one-step route to [18F]CF3SO2NH4 from [18F]fluoride, and its appli...
Article
Single electron reduction is more challenging for sulfamoyl chlorides than sulfonyl chlorides. However, sulfamoyl and sulfonyl chlorides can be easily activated by Cl-atom abstrac-tion by a silyl radical with similar rates. This later mode of acti-vation was therefore selected to access aliphatic sulfonamides applying a single-step hydrosulfamoylat...
Article
An operationally simple method enabling hydrochlorofluoromethylation of unactivated alkenes under visible light activation is reported. The procedure has various benefits. It uses commercially available and inexpensive chlorofluoroacetic acid and phenyliodine(III) diacetate for the generation of the required chlorofluoromethyl radical, it converts...
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Translocator protein (TSPO) expression is increased in activated glia, and has been used as a marker of neuroinflammation in PET imaging. However, the extent to which TSPO upregulation reflects a pro- or anti-inflammatory phenotype remains unclear. Our aim was to determine whether TSPO upregulation in astrocytes and microglia/macrophages is limited...
Article
Die direkte Fluorierung von C‐H‐Bindungen eröffnet den Zugang zu hochfunktionalisierten Molekülen wie Pharmazeutika oder PET‐Radiotracern. Dieser Aufsatz gibt einen Überblick über den Status quo dieses Gebietes, unter Betonung der Vorzüge und Nachteile der aktuell verfügbaren Aktivierungsmodi. Die Diskussion unterstreicht die Wichtigkeit der Art de...
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This Review summarizes the advances in fluorination via C(sp2)–H and C(sp3)–H activation. Transition metal catalyzed approaches championed by palladium have allowed the installation of a fluorine substituent at C(sp2) and C(sp3) sites exploiting the reactivity of high oxidation transition metal fluoride complexes combined with the use of directing...
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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...
Article
Potassium fluoride (KF) is an ideal reagent for fluorination because it is safe, easy to handle and low-cost. However, poor solubility in organic solvents coupled with limited strategies to control its reactivity has discouraged its use for asymmetric C–F bond formation. Here, we demonstrate that hydrogen bonding phase transfer catalysis with KF pr...
Article
A novel highly reactive electrophilic bromodifluoromethylthiolating reagent, α‐cumyl bromodifluoro‐methanesulfenate 1, was prepared to allow for direct bromodifluoromethylthiolation of aryl boron reagents. This coupling reaction takes place under copper catalysis, and affords a large range of bromodifluoromethylthiolated arenes. These compounds are...
Article
A novel highly reactive electrophilic bromodifluoromethylthiolating reagent, α‐cumyl bromodifluoro‐methanesulfenate 1, was prepared to allow for direct bromodifluoromethylthiolation of aryl boron reagents. This coupling reaction takes place under copper catalysis, and affords a large range of bromodifluoromethylthiolated arenes. These compounds are...
Article
The conformations adopted by urea and thiourea functional groups influence catalysis and binding. We combine data-mining with quantum chemical calculations to understand the differences in conformational behavior for these two important structural motifs. We developed a Python tool to automate the compilation of X-ray structural information and per...
Article
Full-text available
PARP inhibitors are increasingly being studied as cancer drugs, as single agents or as a part of combination therapies. Imaging of PARP using a radiolabeled inhibitor has been proposed for patient selection, outcome prediction, dose optimization, genotoxic therapy evaluation, and target engagement imaging of novel PARP-targeting agents. Here, via t...
Article
Aryl substituted 2,2,2-trifluorodiazoethanes undergo rhodium(II)-catalysed insertion reactions with tin hydrides affording the corresponding α-(trifluoromethyl)benzyl stannanes. This reactivity contrasts with that of diazo esters which predominantly afford CH2 reduction products in the presence of tin hydrides. The first example of asymmetric inser...
Article
Radiolabelled (bio)molecules have advanced many areas of science from fundamental biology to human health including applications in molecular imaging and more generally nuclear medicine. Today, the field of radiochemistry is rapidly expanding, a trend resulting from the increasing demand for labelled molecules necessary for diagnosis and to acceler...
Article
H-bond to deliver fluoride Simple fluoride salts are theoretically convenient reagents for carbon-fluorine bond formation. In practice, they are often insoluble in the solvents that dissolve their reaction partners. Pupo et al. developed urea-based catalysts that make fluoride soluble through hydrogen bonding. Moreover, their chiral substituents bi...
Article
A novel protocol for the regio- and stereoselective iodofluorination of internal and terminal alkynes using 1,3-diiodo-5,5,-dimethylhydantoin and HF-based reagents is disclosed. This approach is used to prepare a fluorinated tamoxifen derivative in two steps from commercially available starting materials. A facile method enabling controlled regiose...
Article
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A highly diastereoselective synthesis of trifluoromethyl-substituted indolines under palladium catalysis is disclosed. The reaction proceeds by interceptive decarboxylative benzylic cycloaddition (IDBC) of nonvinyl, trifluoromethyl benzoxazinanones with sulfur ylides. The palladium−π-benzyl zwitterionic intermediates are suggested for this transfor...
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Full-text available
The incorporation of fluorine can not only significantly facilitate the study of proteins but also potentially modulate their function. Whilst some biosynthetic methods allow global residue-replacement methods, post-translational fluorination would constitute a fast and efficient alternative. Here, we reveal a mild method for direct protein radical...
Article
The 18F-labeling of 5-(trifluoromethyl)dibenzothiophenium trifluoromethanesulfonate, commonly referred to as the Umemoto reagent, has been accomplished applying a halogen exchange 18F-fluorination with 18F-fluoride, followed by oxidative cyclization with Oxone® and trifluoromethanesulfonic anhydride. This new 18F-reagent allows for the direct chemo...
Article
Conventional bulk radical co- and terpolymerizations of α-fluoromethylstyrene (FMST) or/and α-trifluoromethylstyrene (TFMST) with styrene (ST) initiated by α,α’-azobis(isobutyronitrile) (AIBN) are presented. The resulting poly(F-ST-co-ST) copolymers and poly(TFMST-ter-ST-ter-FMST) terpolymers were characterized...
Article
Molecules labeled with fluorine 18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a signific...
Article
In this work, we describe the (18)F-labeling of α,α-difluoro-α-(aryloxy)acetic acid derivatives and demonstrate that these building blocks are amenable to post-(18)F-fluorination functionalization. Protodecarboxylation offers a new entry to (18)F-difluoromethoxyarene, and the value of this approach is further demonstrated with coupling processes le...
Article
As compared to the drug discovery process, the development of new 18F PET tracers lacks a well-established pipeline that advances compounds from academic research to candidacy for (pre)clinical imaging. In order to bridge the gaps between methodological advances and clinical success, we must rethink the development process from training to implemen...
Article
The typically planar amide when incorporated into bicyclic systems can undergo a significant distortion from planarity resulting in physical properties and reactivity that deviate from classical amide behaviour. Herein, we report a succinct protocol that utilises potassium permanganate to selectively α-oxygenate the benzylic position of ethano-Trög...
Article
The synthesis and radical co- and terpolymerizations of α-trifluoromethylstyrene (TFMST) with various fluorinated and hydrogenated comonomers are presented. The selected fluorinated comonomers were: vinylidene fluoride (VDF), chlorotrifluoroethylene (CTFE), 3,3,3-trifluoropropene (TFP), 1H,1H,2H,2H-perfluoro-1-decyl vinyl ether (FAVE-8), while the...
Article
A general method for the copper mediated nucleophilic (123)I-iodination of (hetero)aryl boronic esters and acids has been developed. The broad substrate scope of this radiosynthetic approach allows access to [(123)I]DPA-713, [(123)I]IMPY, [(123)I]MIBG and [(123)I]IPEB that are four commonly used SPECT radiotracers. Our results infer that aryl boron...
Article
Full-text available
Alkenes substituted with a thiourea undergo C–CF 3 followed by intramolecular C–S bond formation with the Togni reagent and trifluoroacetic acid (TFA) at room temperature; thiols and thioamides are not suitable S-sources for this reaction. This anti-addition process involves a CF 3 radical, and affords CF 3-substituted thiazolines and thiazines for...