Developing access to new molecules is a key objective for chemists, particularly to three-dimensional, sp3-rich compounds which show improved bioactivity compared with flatter structures favoured by recent strategies within the pharmaceutical sector. Although this importance is known there remains a lack of reliable methodologies for creating this diversity; traditional metal-catalysed cross-coupling processes show a great ability to form bonds but remain associated with flat molecular architectures. However, great potential to form complex three-dimensional structures has been shown by the application of transition metal catalysis to the release of inbuilt ring strain. In particular, the use of tandem reactions involving this approach has proved to be a powerful of forming complex, drug-like molecules in only one or two steps.
Work at Northumbria has developed efficient syntheses of strained two-carbon building blocks, designed to allow ring-opening using a photo-redox catalyst rather than a transition metal. Appropriate pre-functionalisation will allow the resulting products to undergo further photoredox processes within the same reaction flask, leading to cascade processes not dissimilar to those described above. Such work will build on a growing interest in light-driven chemical synthesis, and create new pathways for the productive release of ring strain. Further, the resulting molecules will possess greater structural complexity than those resulting from traditional approaches. Results will be disseminated via high impact journals, and compounds formed will undergo biological testing against cellular targets (cancer, bacterial, CNS) through collaboration with groups at Northumbria University and the University of Bristol. While the scale of photoredox catalysis reactions has traditionally been limited, Northumbria University has access to visible light macro-flow reactors and expertise in using them. This will allow successful reactions to produce multiple grams of material, permitting further derivatisation of compounds that show promise in preliminary biological testing and the initiation of a programme of medicinal chemistry around them.
Eligibility and How to Apply:
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required.
• Applicants cannot apply for this funding if currently engaged in Doctoral study at Northumbria or elsewhere.
For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/ Please note: Applications should include a covering letter that includes a short summary (500 words max.) of a relevant piece of research that you have previously completed and the reasons you consider yourself suited to the project. Applications that do not include the advert reference (e.g. SF20/…) will not be considered.
Deadline for applications: 1st July for October start, or 1st December for March start
Start Date: October or March
Northumbria University takes pride in, and values, the quality and diversity of our staff. We welcome applications from all members of the community. The University holds an Athena SWAN Bronze award in recognition of our commitment to improving employment practices for the advancement of gender equality.
Please direct enquiries to Dr Jon Knowles (
[email protected])
References
1) For an example from my own work, see: C. J. Gerry, B. K. Hua, M. J. Wawer, J. P. Knowles, S. D. Nelson, Jr., O. Verho, S. Dandapani, B. K. Wagner, P. A. Clemons, K. I. Booker-Milburn, Z. V. Boskovic, S. L. Schreiber, J. Am. Chem. Soc., 2016, 138, 8920. 2) a) K. G. Maskill, J. P. Knowles, L. D. Elliott, R. W. Alder and K. I. Booker-Milburn, Angew. Chem. Int. Ed., 2013, 52, 1499; b) J. P. Knowles and K. I. Booker-Milburn, Chem. Eur. J., 2016, 22, 11429; c) P. J. Koovits, J. P. Knowles and K. I. Booker-Milburn, Org Lett., 2016, 18, 5608. 3) E. E. Blackham, J. P. Knowles, J. Burgess and K. I. Booker-Milburn, Chem. Sci, 2016, 7, 2302. 4) L. D. Elliott, J. P. Knowles, P. J. Koovits, K. G. Maskill, M. J. Ralph, G. Lejeune, L. J. Edwards, R. I. Robinson, I. R. Clemens, B. Cox, D. D. Pascoe, G. Koch, M. Eberle, M. B. Berry and K. I. Booker-Milburn, Chem. Eur. J., 2014, 20, 15226; b) L. D. Elliott, J. P. Knowles, C. S. Stacey, D. J. Klauber and K. I. Booker-Milburn, React. Chem. Eng., 2018, 3, 86.
