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Details of Grant 

EPSRC Reference: EP/R008795/1
Title: Automating the Synthetic Chemistry Landscape in Bristol: Accelerating Impact and Application
Principal Investigator: Aggarwal, Professor VK
Other Investigators:
Canagarajah, Professor N Butts, Professor CP
Researcher Co-Investigators:
Project Partners:
Chemspeed Technologies Ltd
Department: Chemistry
Organisation: University of Bristol
Scheme: Standard Research
Starts: 01 September 2017 Ends: 31 August 2027 Value (£): 766,927
EPSRC Research Topic Classifications:
Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
11 Jul 2017 EPSRC Strategic Equipment Interview Panel July 2017 Announced
Summary on Grant Application Form
In universities across the UK, research devoted to chemical synthesis is traditionally pursued one reaction at a time leading to an average of one reaction being conducted per day per person. Therefore, an unacceptably large portion of time, manpower and consumables is devoted to the routine yet necessary tasks of reaction optimisation, the exploration of substrate scope and the synthesis of molecular libraries. A large and disproportionate amount of time is spent low-value activities such as handling, preparation and data collection rather than on high-value activities such as the actual reaction and the subsequent analysis and interpretation of results. Access to an automated workstation would significantly increase the efficiency, output and quality of these tasks thus allowing valuable resource to be reallocated to problem-solving, innovation and application.

The development of simple and robust automated methods for peptide and oligonucleotide (and to some extent oligosaccharide) synthesis revolutionised the field enabling complex proteins and DNA/RNA oligomers to be prepared routinely and studied. These types of methodology were so useful that they were recognised by the award of Nobel prizes to the discoverers (Merrifield, 1984; Todd, 1957, Khorana 1968). We plan to employ recently created robust methodology that has been created in the UK and world-wide and adapt its employment on an ISYNTH Automated Workstation. This fully automated and programmable workstation can setup (dispense solids and liquids), run, and workup as many as 96 reactions at a time (up to an 8 mL volume for each vessel). The workstation can then purify products (through an aqueous extraction module or through a filtration module) and subject them as starting materials for further reactions (through automated evaporation and dissolution in fresh solvent), thus enabling multistep synthesis of libraries of molecules. The reactions can be set up under an inert atmosphere, under high pressure of reactive gases, at any temperatures from -70 C to +200 C and will be interfaced with an ultra-high-performance liquid chromatography/mass spectrometry (UHPLC-MS) for rapid and high-throughput in-line (online) analysis of reaction mixtures. The envisaged set-up is thus capable of automating most types of reactions that are employed in modern synthesis. For the user, it involves just loading raw materials, keying in a set of commands and walking away. If, even a fraction of organic synthesis can be conducted in this way it could have as big an impact as automated peptide and oligonucleotide synthesis.

Automating the optimisation of organic reactions and automating the synthesis of compound libraries will improve efficiency and throughput dramatically. Furthermore, the increased high-quality data that will emerge from optimisation reactions will feed into multi dimension computations that ultimately will be used to design and predict reaction outcomes. The synergy between high-quality reaction setup, data collection, analysis and computation, which will be key components of our facility, will enable such predictions to become meaningful.

Key Findings
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Potential use in non-academic contexts
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Further Information:  
Organisation Website: http://www.bris.ac.uk