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Details of Grant 

EPSRC Reference: EP/Y00146X/1
Title: Organoborane-catalysed approaches to biologically active amines
Principal Investigator: Pulis, Dr A P
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Concept Life Sciences
Department: Chemistry
Organisation: University of Leicester
Scheme: New Investigator Award
Starts: 01 October 2023 Ends: 30 September 2026 Value (£): 455,776
EPSRC Research Topic Classifications:
Catalysis & Applied Catalysis Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:
Chemicals Pharmaceuticals and Biotechnology
Related Grants:
Panel History:
Panel DatePanel NameOutcome
03 May 2023 EPSRC Physical Sciences Prioritisation Panel - May 2023 Announced
Summary on Grant Application Form
In order to discover a new medicine, academic and industrial researchers require access to diverse collections of molecules. However, the slow step in medicine discovery is the synthesis of these biologically active molecules from simpler building blocks. In many cases, key molecules are inaccessible with current technologies, which prevents researchers exploring the full range of chemical structures required to understand and develop a new medicine. Around 80% of the molecules used in the drug discovery process contain a nitrogen atom (in the form of amines), and therefore novel methods that generate new amine structures are highly valued in the drug discovery arena.

In this project, we will explore the unique reactivity of organoboranes to develop a novel and general catalytic platform for the synthesis of amines. Organoboranes have an unusual ability to abstract hydride from amines, generating a reactive cationic intermediate and a hydride bound to boron. This unique reactivity will allow common and readily available building blocks to be used in novel processes. The methods discovered in the project will be easy to use and not require special training. It will also generate low waste through high atom economy. The project will demonstrate the utility of these new tools to targeted end-users in academia, and pharmaceutical and supporting Contract Research industries, by solving specific challenges in drug discovery. For example, by addressing limitations in the synthesis of nitrogen-containing molecules, we will enable access to new and previously inaccessible structures. This will transform medicinal and biological chemists' abilities by enabling them to develop clear pictures of structure-activity relationships that are critical for studying disease and developing new treatments.

The project is divided into three Aims that represent the three reaction classes where we will employ the unique abilities of organoboranes to solve challenges.

- Aim 1 will target the first direct and modular synthesis of privileged aryl alkyl amines found in serotonergic/dopaminergic pharmaceuticals that treat a variety of mental illnesses. This Aim will enable efficient access to aryl alkyl amines and allow a full and systematic study of how structure affects activity and therefore lead to more efficacious treatments.

- Aim 2 will develop a new approach to the catalytic alpha CH arylation of amines. We will demonstrate utility of this method in the late-stage-functionalisation of a variety of validated medicines so that new or improved bioactivity can be efficiently discovered from known molecular templates.

- Aim 3 will develop a new approach to the synthesis of a common class of bioactive N- heterocycles, tetrahydroquinolines. We will address specific limitations of current methods and will enable the rapid exploration of chemical space for structure activity relationships related to treatments for cancer, pain, osteoporosis, parasite infections and allergies for the first time.

Key Findings
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Organisation Website: http://www.le.ac.uk