PhD Studentship - Benzofused Azabicycles and Spiropiperidines via Biocatalytic Oxidation-Cycloa

Project Details

Research theme: Biocatalysis, Bioorganic Chemistry. 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.

o‑Quinoid species (e.g. quinones, quinone imines, quinone methides) are versatile reactive intermediates for the synthesis of a variety of complex molecules. They readily undergo a range of reactions including 1,4‑conjugate additions, 1,3‑oxazole formation, and Diels–Alder cycloadditions, with particular interest because these reactions 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. 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. The research will investigate the following: (1) the synthetic scope of these reactions; (2) the 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, the aim is to develop more sustainable methods for the production of high‑value organic compounds.

The 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 join a 4‑year doctoral programme at the Manchester Institute of Biotechnology, which offers state‑of‑the‑art laboratories, instrumentation and facilities. They will also be part of the Bio Process Biocatalysis and Protein Engineering Centre for Sustainable Synthesis, which has strong partnerships with the chemical industry, and will receive broad scientific training across chemistry, molecular biology and chemical engineering, as appropriate to their background.

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

The successful candidate will receive a tax‑free annual stipend of £21,805 for 2026/27, with the stipend increasing each year, and tuition fees will be paid throughout the four‑year programme.