Electrochemical fluorodecarboxylation for the labelling of gem-difluoro(cyclo)alkanes/amines
Lead Research Organisation:
University of Oxford
Department Name: Oxford Chemistry
Abstract
Positron emission tomography (PET) is a powerful molecular imaging modality for diagnosis, monitoring disease progression, studying biological processes in vivo, and investigating the efficacy of drugs. Among the radioisotopes employed for the preparation of PET probes, fluorine-18 is a widely used and clinically relevant radionuclide in part due to its favourable decay properties, and the numerous clinical applications. While radiochemists have in recent years focused their efforts on methods enabling 18F-labelled fluorination and trifluoromethylation of (hetero)arenes, 18F-radiolabelled gem-difluorinated reactions have been much less studied despite the importance of the gem-difluoromethylene group (CF2) in radioligand design for drug discovery programmes. Herein, we propose a solution merging electrochemistry and 18F radiochemistry with the development of a novel electrochemical fluorodecarboxylation process affording 18F-labelled gem-difluoro(cyclo)alkanes and (cyclo)amines including structurally complex pharmaceutical drugs.
Organisations
| Description | We have developed a novel method to access medicinally relevant geminal difluoro motif in unactivated substrates via fluorodecarboxylation of a-fluoro carboxylic acids. Specifically, the method makes use of a manganese porphyrin system, iodosobenzene and a soluble fluoride reagent. An electrochemical variant of this process is currently under investigation. This work led to a serendipitous discovery dealing with perfluorinated substances, and the development of a technology that led to a licensed patent. A paper has been accepted in nature, still under embargo. |
| Exploitation Route | Application in pharmaceutical drug discovery for patient care, and a new technology to prepare pharmaceuticals from waste PFAS. |
| Sectors | Chemicals Environment Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | The geminal difluoro motif is widely present in pharmaceutical molecules, most often to improve metabolic stability and fine-tune lipophilicity. Despite its prevalence, there is a significant lack of methods for the preparation of these motifs and more specifically to access 18F-variant for applications in Positron Emission Tomography. Fluorodecarboxylation has proven to be a powerful method for the incorporation of fluorine into organic molecules. However, these methods are limited to activated substrates and employ an inconvenient electrophilic fluorine source or were not translatable to 18F radiofluorination. This grant has enabled the invention of novel oxidative fluorodecarboxylation processes to prepare molecules with gem-difluoro motifs from fluoride sources (19F and 18F). The postdoc appointed on the award made in the lab a serendipitous discovery that led him to develop a method to destroy PFAS (licensed patent and paper in Nature accepted but under embargo) |
| First Year Of Impact | 2024 |
| Sector | Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal Economic |
| Title | PFAS destruction |
| Description | A new method for PFAS destruction |
| IP Reference | |
| Protection | Patent / Patent application |
| Year Protection Granted | 2024 |
| Licensed | Yes |
| Description | 2023 Bohlmann Lecture - TU Berlin (Germany) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2023 |
| Description | 2023 EuChemS Female Organic Chemist of the Year Award Lecture- Bayer AG (Germany) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2023 |
| Description | 2023 George Büchi Lectureship, MIT - Cambridge (USA) |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2023 |
| Description | 38th Annual H. C. Brown Lectures - Purdue University West Lafayette (USA) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2023 |
| Description | Cambridge AstraZeneca Lecture (UK) |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2023 |
| Description | Gassman Lectureship - University of Minnesota (USA) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2023,2024 |
| Description | Manchot Research Professorship, Technische Universitaet Muenchen (Germany) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2022 |
| Description | National Historic Chemical Landmark Symposium Lecture - Indiana University (USA |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2024 |
| Description | Novartis Lectureship (x 2) (Basel - Switzerland -virtual, Cambridge - USA) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2022 |
| Description | Rowland Petitt Centennial Visiting Professorship - UT Austin (USA) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2025 |
| Description | SCI Process Chemistry Award Lecture - Cambridge, UK |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2023,2024 |
| Description | The Beckman Lecture - California Institute of Technology (USA) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2024 |
| Description | The Chemical Record Lecture - Chemical Society of Japan (Japan) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2024 |
| Description | The Karl Ziegler Lectures - Max-Planck-Institut für Kohlenforschung (Germany) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | vg to complete |
| Year(s) Of Engagement Activity | 2023,2024 |
| Description | The Ojima Distinguished Lectureship, Guest Lecture and Award - Stonybrook University, New York (USA) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | VG TO COMPLETE |
| Year(s) Of Engagement Activity | 2025 |