C-H Activation/functionalisation approaches to building blocks for discovery applications
Lead Research Organisation:
University of Leeds
Department Name: Sch of Chemistry
Abstract
Context of research: The discovery of bioactive small molecules is an enduring challenge in both medicinal chemistry and chemical biology. Yet, chemists' exploration of chemical space has historically been highly uneven and unsystematic, with over a sixth of known compounds being based on just 30 (out of 2.5 million) molecular frameworks. Furthermore, despite an increased understanding of the impact of specific molecular properties of discovery applications, new synthetic methods tend not to deliver building blocks with optimal properties for discovery applications. Indeed, a remarkably small toolkit of reactions underpins discovery, tending to drive chemists away from ideal property space (e.g. towards more lipophilic and flatter compounds in drug discovery). To address this, new (sequences of) chemical transformations capable of delivering molecules with more tightly-controlled molecular properties are required.
Aims and objectives: This project aims to leverage regioselective C-H activation chemistry on saturated nitrogen heterocycles to (a) facilitate direct growth of small molecule'fragments'; (b) create high value/unknown heterocyclic building blocks from simple (commercial where possible) compounds; and (c) leverage downstream functionalisation chemistry (such as direct photochemical aromatic amination chemistry) to create unique 3D scaffolds with unusual physicochemical properties likely to make them of value to practitioners in the discovery of bioactive compounds. Initially, the project will exploit regioselective electrochemical oxidation as the platform C-H activation, but alternative photochemical and/or catalytic approaches may be investigated as the project develops. The project will make use of the computational tool LLAMA (www.llama.leeds.ac.uk) previously developed using EPSRC funding to prospectively identify the most promising/relevant transformations and targets, and to prioritise these.
Potential applications and benefits: This industrially-linked studentship will provide an excellent training in the design and development of new synthetic methods (including catalytic reactions), coupled with an awareness of the importance of controlling molecular properties for discovery applications. The industrial placement will give the student experience of technology transfer between academia and industry, as well as a better understanding of the commercial drivers for technology companies.
Research areas: Synthetic organic chemistry; Chemical biology and biological chemistry; Catalysis
Qualification to be obtained: PhD in Organic Chemistry
Aims and objectives: This project aims to leverage regioselective C-H activation chemistry on saturated nitrogen heterocycles to (a) facilitate direct growth of small molecule'fragments'; (b) create high value/unknown heterocyclic building blocks from simple (commercial where possible) compounds; and (c) leverage downstream functionalisation chemistry (such as direct photochemical aromatic amination chemistry) to create unique 3D scaffolds with unusual physicochemical properties likely to make them of value to practitioners in the discovery of bioactive compounds. Initially, the project will exploit regioselective electrochemical oxidation as the platform C-H activation, but alternative photochemical and/or catalytic approaches may be investigated as the project develops. The project will make use of the computational tool LLAMA (www.llama.leeds.ac.uk) previously developed using EPSRC funding to prospectively identify the most promising/relevant transformations and targets, and to prioritise these.
Potential applications and benefits: This industrially-linked studentship will provide an excellent training in the design and development of new synthetic methods (including catalytic reactions), coupled with an awareness of the importance of controlling molecular properties for discovery applications. The industrial placement will give the student experience of technology transfer between academia and industry, as well as a better understanding of the commercial drivers for technology companies.
Research areas: Synthetic organic chemistry; Chemical biology and biological chemistry; Catalysis
Qualification to be obtained: PhD in Organic Chemistry