Accelerated Synthesis of Agrochemicals and Pharmaceuticals (ASAP): Bridging the Gap Between Research and Application
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Chemistry
Abstract
Food and healthcare are the foundations on which our current quality of life is built. The pressure on these resources will only increase as the UK population ages, the global population reaches 9 billion in 2050 and the worst effects of climate change begin to manifest. Now more than ever, new medicines and agrochemicals will be vital in combating the growing and evolving threats that face society. A major challenge to the development of new medicines and agrochemicals is the high attrition rate of the candidate molecules being investigated, which drives up the financial cost, environmental impact and time associated with bringing a new product to market. Methods that allow rapid cost- and resource efficient preparation of desirable candidate molecules are therefore extremely valuable.
This programme will deliver a suite of synthesis methods to streamline the discovery and development of the next generation of agrochemicals and pharmaceuticals. Building on our recent discovery, we will develop new ways of making valuable molecular architectures while minimising the number of chemical operations required and avoiding the use of toxic or precious elements. By working in close collaboration with leading innovators in crop protection (Syngenta) and human healthcare (AstraZeneca, Pfizer and Carbometrics), we will ensure that our methods will be of direct and immediate benefit. We will also seek to make the reagents we develop commercially available, thus further enabling the rapid and barrierless uptake of our methods.
This programme will deliver a suite of synthesis methods to streamline the discovery and development of the next generation of agrochemicals and pharmaceuticals. Building on our recent discovery, we will develop new ways of making valuable molecular architectures while minimising the number of chemical operations required and avoiding the use of toxic or precious elements. By working in close collaboration with leading innovators in crop protection (Syngenta) and human healthcare (AstraZeneca, Pfizer and Carbometrics), we will ensure that our methods will be of direct and immediate benefit. We will also seek to make the reagents we develop commercially available, thus further enabling the rapid and barrierless uptake of our methods.
Publications
Calcatelli A
(2022)
Modular Synthesis of a,a-Diaryl a-Amino Esters via Bi(V)-Mediated Arylation/SN2-Displacement of Kukhtin-Ramirez Intermediates.
in Organic letters
Dalligos D
(2023)
Coaxial Dielectric Spectroscopy as an In-Line Process Analytical Technique for Reaction Monitoring
in Organic Process Research & Development
Fox A
(2024)
Development and Scale-Up of a New Sulfone-Based Bismacycle as a Universal Precursor for Bi(V)-Mediated Electrophilic Arylation.
in Organic process research & development
Joynson B
(2023)
Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment
in Angewandte Chemie
Joynson B
(2023)
Skeletal Editing: Interconversion of Arenes and Heteroarenes
in Helvetica Chimica Acta
Joynson BW
(2023)
Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment.
in Angewandte Chemie (International ed. in English)
Ruffell K
(2022)
Umpolung Synthesis of Pyridyl Ethers by Bi V -Mediated O-Arylation of Pyridones
in Angewandte Chemie
Ruffell K
(2022)
Umpolung Synthesis of Pyridyl Ethers by Bi V -Mediated O-Arylation of Pyridones
in Angewandte Chemie International Edition
Ruffell K
(2022)
Bismuth-Mediated a-Arylation of Acidic Diketones with ortho -Substituted Boronic Acids
in Angewandte Chemie
Related Projects
| Project Reference | Relationship | Related To | Start | End | Award Value |
|---|---|---|---|---|---|
| MR/V022067/1 | 01/03/2022 | 30/07/2025 | £1,390,804 | ||
| MR/V022067/2 | Transfer | MR/V022067/1 | 30/07/2025 | 29/07/2029 | £0 |
| Description | We have developed synthesis methods based on non-toxic bismuth which enable the efficient preparation of new molecules that have potential applications in drug discovery or agrochemical development. These methods include: - streamlined synthesis of 2-arylcyclohexadiones, which are an important motif in herbicides. Our method has the potential to replace traditional processes based on toxic lead/mercury reagents. - streamlined synthesis of aryloxypyridines, which are an important substructure of several anticancer drugs. - introduction of new chemical reactivity that formally overturns a traditional selectivity dogma. - development of a new tool for monitoring the progress of reactions, with potential applications in safer / more efficient manufacturing. - development of a method for chemically 'upgrading' lignin-derived biomass feedstocks into more valuable molecules. |
| Exploitation Route | Our contributions to dione and pyridone arylation may allow agrochemical / pharmaceutical discovery chemists to make new molecules more quickly and more efficiently, thereby expediting development of the next generation of medicines and crop-protection products. Our work on reaction monitoring has received interest from the pharmaceutical and commodity chemicals sector as a low-cost method for following chemical processes, which complements existing methods. |
| Sectors | Chemicals Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
| Description | One of the methods developed in our lab has been applied by an agrochemical company to prepare new molecules for field testing. |
| First Year Of Impact | 2023 |
| Title | CCDC 2171727: Experimental Crystal Structure Determination |
| Description | Related Article: Katie Ruffell, Stephen P. Argent, Kenneth B. Ling, Liam T. Ball|2022|Angew.Chem.,Int.Ed.|61|e202210840|doi:10.1002/anie.202210840 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc2bwvqt&sid=DataCite |
| Description | Computational Bi Collaboration |
| Organisation | Colorado State University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We provided experimental results and expertise of the research field. |
| Collaborator Contribution | Expertise in computational modelling |
| Impact | 10.1002/anie.202212873 |
| Start Year | 2021 |
