Bioinspired Total Synthesis of Complex Natural Products

Supervisory Team: Dr Jonathan George

This project will involve the total synthesis of stereochemically complex natural products using new methods inspired by biosynthesis. The synthetic work will have potential applications in medicinal chemistry, the elucidation of biosynthetic pathways, and the structural assignment of natural products. 

Background:

The use of natural products as antibiotics and anticancer agents has revolutionised human healthcare. However, many natural products are highly complex molecules isolated in minute amounts from their natural source. The total synthesis of these molecules is therefore crucial to allow their future application in medicine. This research project aims to develop new ways of constructing 3-dimensionally complex natural products using strategies inspired by their biosynthesis. In particular, we will target the synthesis of natural products of mixed biosynthetic pathways in which the dearomatization of aromatic rings converts simple, flat structures into stereochemically complex molecules. This work will expand the toolkit of complexity-generating organic reactions that can be applied in medicinal chemistry.

Research in the George Group: 

We have developed many concise, biomimetic total syntheses of complex molecules – summarised in the following review (Acc. Chem. Res. 2021 https://pubs.acs.org/doi/10.1021/acs.accounts.1c00019). 

Sometimes our syntheses help to decipher biosynthetic pathways in collaboration with biochemists (Nat. Chem. 2017 https://www.nature.com/articles/nchem.2829; Angew. Chem. Int. Ed. 2018 https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201804351). We have also integrated modern methods of photoredox catalysis (Angew. Chem. Int. Ed. 2019 https://onlinelibrary.wiley.com/doi/10.1002/anie.201814089), photochemistry (J. Am. Chem. Soc. 2022 https://pubs.acs.org/doi/10.1021/jacs.2c09978) and biocatalysis (Angew. Chem. Int. Ed. 2019 https://onlinelibrary.wiley.com/doi/10.1002/anie.201812432) into our total synthesis projects. 

Many of our projects involve the biosynthetically-inspired structure revision of natural products (Angew. Chem. Int. Ed. 2022 https://onlinelibrary.wiley.com/doi/full/10.1002/anie.202200420), and even the prediction and isolation of new natural products. Our ultimate goal is to discover new ways to make complex natural products as quickly and easily as possible – sometimes achieving this in just one step! (Chem. Sci. 2023 https://pubs.rsc.org/en/Content/ArticleLanding/2023/SC/D2SC05377B). 

You will receive expert training in synthetic organic chemistry and other specialist areas as required by the project, either from the George Group or appropriate collaborators. You will also gain extensive experience of a range of analytical techniques including advanced NMR analysis and single crystal x-ray diffraction. Mentorship in writing high-impact publications and delivering engaging scientific presentations will also be provided. 

Entry Requirements

A very good undergraduate degree (at least a UK 2:1 honours degree, or its international equivalent).

Closing date: 31 August 2025. Applications will be considered in the order that they are received, the position will be considered filled when a suitable candidate has been identified.

Funding: We offer a range of funding opportunities for both UK and international students, including Bursaries and Scholarships. For more information please visit PhD Scholarships nearmejobs.eu Doctoral College nearmejobs.eu University of Southampton Funding will be awarded on a rolling basis, so apply early for the best opportunity to be considered.

How To Apply

Apply online:  Search for a Postgraduate Programme of Study (soton.ac.uk) Select programme type (Research), 2025/26, Faculty of Engineering and Physical Sciences, next page select “PhD Chemistry. (Full time)”. In Section 2 of the application form you should insert the name of the supervisor Dr Jonathan George

Applications should include:

Research Proposal

Curriculum Vitae

Two reference letters

Degree Transcripts/Certificates to date

For further information please contact: feps-pgr-apply@soton.ac.uk

The School of Chemistry. is committed to promoting equality, diversity inclusivity as demonstrated by our Athena SWAN award. We welcome all applicants regardless of their gender, ethnicity, disability, sexual orientation or age, and will give full consideration to applicants seeking flexible working patterns and those who have taken a career break. The University has a generous maternity policy, onsite childcare facilities, and offers a range of benefits to help ensure employees’ well-being and work-life balance. The University of Southampton is committed to sustainability and has been awarded the Platinum EcoAward.