The sulfoximine functional group is becoming increasingly popular within medicinal chemistry groups – notably, sulfoximines have featured in potential cancer treatments in clinical trials such as AZD6738 developed by AstraZeneca.[1,2] Consequently, there is great interest in developing new synthetic methodology to access structurally diverse sulfoximines. However, there are very limited examples that allow cyclic sulfoximines to be functionalised. In order to explore new areas of 3-D pharmaceutical space, we will explore general methodology for the stereoseective arylation of cyclic sulfoximines. This will deliver novel 3-D sulfoximines for use in medicinal chemistry, via the O’Brien group’s links with the pharmaceutical industry (AstraZeneca, Pfizer, Asahi Kasei).
1. Arylation of 5-ring cyclic sulfoximines at the 2- and 3-positions
2. Arylation of 6-ring cyclic sulfoximines at the 2-, 3- and 4-positions
3. Explore applications of 3-D cyclic aryl sulfoximines in medicinal chemistry
There are three stages to this project, all of which require different types of synthetic methodology development. First, methods will need to be developed to enable the large-scale synthesis of a range of cyclic sulfoximine vinyl bromides/iodides and enol triflates (with different nitrogen protecting groups). Then, their use in a range of medicinally-relevant Suzuki-Miyaura cross-coupling reactions using aryl boronic acids will be studied. Finally, stereoselective hydrogenation will give the stereodefined aryl sulfoximines[3,4] which will be deprotected and be available for use in medicinal chemistry programmes.
There are very few examples of the functionalisation of cyclic sulfoximines and cyclic aryl sulfoximines are an unstudied class of compound.
This project will provide state-of-the-art training in modern synthetic methodology and medicinal chemistry. The graduating PhD student will be fully equipped for a future career in the pharmaceutical industry. All Chemistry research students have access to our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills: https://www.york.ac.uk/chemistry/postgraduate/training/idtc/
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You should hold or expect to achieve the equivalent of at least a UK upper second class degree in Chemistry or a related subject. Please check the entry requirements for your country: https://www.york.ac.uk/study/international/your-country/
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