PhD Studentship - Benzofused Azabicycles and Spiropiperidines via Biocatalytic Oxidation-Cycloaddition Cascades

Research theme: Biocatalysis, Bioorganic Chemistry

How to apply: uom.link/pgr-apply-2425

This 4-year PhD project is fully funded; students who are eligible to pay tuition fees at the Home rate are eligible to apply. The successful candidate will receive an annual tax-free stipend set at the UKRI rate (£21,805 for 2026/27) and tuition fees will be paid. We expect the stipend to increase each year. The start date is October 2026.

We recommend that you apply early as the advert may be removed before the deadline.

o-Quinoid species (e.g. quinones, quinone imines, quinone methides) are versatile reactive intermediates for the synthesis of a variety of complex molecules.[1-4] They readily undergo a range of reactions including 1,4-conjugate additions, 1,3-oxazole formation, and Diels−Alder cycloadditions. The latter reactions of particular interest since they can be used to perform annulations, and hence the rapid construction of multicyclic molecular scaffolds.

We have established that such quinoid intermediates are readily accessible from the corresponding hydroquinoid through biocatalytic oxidation, using either oxidase or peroxidase enzymes.[5,6] Furthermore, we have recently demonstrated that “one pot” tandem reactions can be achieved by combining enzymatic oxidation of o-aminophenols to the quinone imine, and an inverse electron demand Diels-Alder reaction, to give a range of 1,4-benzoxazines. When compared with conventional purely synthetic methods, this biocatalytic route was found to be more sustainable, as evidenced by calculations of the various Green Chemistry metrics.

This project aims to extend this general approach for the synthesis of azabicyclics and spiropiperidines, which are “privileged” scaffolds that are found in various biologically active compounds. This research will investigate the: (1) synthetic scope of these reactions; (2) use of synthetic enzyme cofactors to enable the oxidation of a wide range of quinoid species; (3) directed evolution of enzymes towards high value target compounds. In doing so, we aim to develop more sustainable methods for the production of high value organic compounds.

This research will suit a candidate with a background in chemistry, medicinal chemistry, biological chemistry or related areas. They should have an interest in working on a varied and multidisciplinary project related to synthetic chemistry and biorganic chemistry. The successful candidate will triving research group drawn from a range of backgrounds including chemistry, molecular biology and chemical engineering. They will receive a broad scientific training across these areas, as appropriate to their background. The research group is based in the Manchester Institute of Biotechnology (mib.ac.uk), which offers state-of-the-art laboratories, intrumentation and facilities. They will join a 4-year doctoral programme as part of BioProcess, the Biocatalysis and Protein Engineering Centre for Sustainable Synthesis (bioprocess-idla.ac.uk), which has strong partnerships with the chemical industry. They will thus have the opportunity to participate in a range of programme activities, training and placements.

Applicants should have, or expect to achieve, at least a 2.1. honours degree or Master's (or equivalent) in chemistry or a related subject (see above).

To apply, please contact the main supervisor; Dr Wong. Please include details of your current level of study, academic background and any relevant experience and include a paragraph about your motivation to study this PhD project.

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