Investigating the formation of beta-lactams via asymmetric photochemical Staudinger reactions

Lead Research Organisation: University of Oxford


Modern photoredox catalysis aims to achieve chemical transformations which were hitherto impossible using milder reaction conditions and producing less waste than traditional synthetic chemistry. It does this by using visible light (usually blue), along with a small amount of catalyst (usually containing a transition metal), to perform reactions which may have traditionally necessitated the use of large amounts of chemical reagents, and which may have produced large amounts of waste and unwanted byproducts. The impact of this shift to cleaner methods of synthesis is clear - large scale production of necessary chemicals (pharmaceuticals, agrichemicals, etc.) will have a much lower impact on the environment, a key concern in today's environment.
This project specifically aims to develop a new method of synthesising beta-lactams. Beta-lactams are commonly found in drug molecules and a whole class of antibiotics including penicillin derivatives (penams) contains this type of structure. These types of structure are usually functionalised (they contain some other types of structure chemically bonded to them) and this gives rise to chirality within the molecule. Most reactions cannot discriminate between forming one form (enantiomer) of a product or another. This is a key issue when only one enantiomer is desired as separation of enantiomers is costly and yields are artificially limited. With this project we wish to develop a method which can discriminate between different enantiomers and produce only the desired one, thereby maximising efficiency and minimising waste. Coupling this with efficient photocatalysis improves the reaction even more and small amounts of catalyst can be used which further minimises waste.
While asymmetric photocatalysis is precedented in the literature, many of these make use of two different types of catalyst, increasing the overall amount of catalyst which needs to be used. A number of examples chiral photocatalysts which do not require the use of co-catalysts exist, but these have been used for different purposes and not for chemical structures which are directly relevant to medicinal chemistry and pharmaceuticals. The project will therefore attempt to build on the work done by others in the field on developing chiral photocatalysts and aim to apply it to reactions and reactivity which are directly relevant to challenges faced in modern chemistry.

This project falls within the EPSRC Synthetic Organic Chemistry research area.

Planned Impact

This programme is focused on a new cohort-driven approach to the training of next-generation doctoral scientists in the practice of novel and efficient chemical synthesis coupled with an in-depth appreciation of its application to biology and medicine.

This collaborative academic-industrial SBM CDT will have long-term benefit to the chemical industry, including the pharmaceutical, agrochemical and fine chemical sectors. These industries will benefit through: (i) the potential to employ individuals trained with broad and relevant scientific and transferable skills; (ii) new approaches to the investigation of complex biological and medical problems through novel chemistry; and (iii) better and more efficient synthetic methods.

We will link the work of DSTL, and our pharmaceutical and agrochemical partners (GSK, UCB, Vertex, Evotec, Eisai, AstraZeneca, Syngenta, Novartis, Takeda, Sumitomo and Pfizer) through a common theme of synthesis training. The design and synthesis of new compounds is essential for disease treatment and prevention, and for maintaining food security. Synthesis contributes significantly to UK tax revenue and results in sustained employment across a number of sectors. Employers in the finance, law, health, academic, analytical, government, and teaching professions, for example, also recognise the value of the translational skill-sets possessed by synthesis postgraduates, which this programme will provide.

The SBM CDT training programme will adopt an IP-free model to enable completely free exchange of information, know-how and specific expertise between students and supervisors on different projects and across different industrial companies. This will lead to better knowledge creation through unfettered access to information from all academics, partners and students involved in the project. By focussing on basic science, we will engender genuine collaboration leading to enabling technology that will be of use across a wide range of industries.

We will train the next generation of multidisciplinary synthetic chemists with an appreciation of the impact of synthesis in biology and medicine. Their unconstrained view of synthesis will aid in new scientific discoveries leading to new products, which (with appropriate inward investment), can lead to the formation of new companies and new UK employment.

We will, in part through an alliance with the Defence, Science and Technology Laboratory, engage with policy-makers to influence future policy issues involving chemistry such as food security and the rise of antibiotic resistance (both of which are relevant to our programme and are important for society as a whole).

Outreach and public engagement will be a key aspect of our programme; and all students in the proposed SBM CDT will take part in at least one outreach activity. Typical activities include: open days in the Chemistry Department through the 'Outreach Alchemists', engaging with the Oxfordshire Science Festival and participation in the various other activities already in place through the public engagement programme of the Department of Chemistry.

The research output of the students will be disseminated via high impact international publications and lectures; these will be of value to other academics in relevant fields and will be of value in the development of further research funding applications. Outreach activities and research output will also be advertised on a website dedicated to the proposed SBM programme.


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