Taking Inspiration from Nature for the Synthesis of Natural Products and Analogues

Natural products and their derivatives continue to be important as leads for the discovery of new biologically active compounds as well as an inspiration for novel strategies in organic synthesis.

This project builds upon preliminary results from investigations into the biosynthesis of the antibiotic abyssomicin C. It will include studies on the biosynthetic pathway to abyssomicin C and related compounds in which a Diels-Alder reaction is critical to assembly of the complex molecules. A combination of organic synthesis, spectroscopy and biotransformations will be used leading to clean and efficient methods to access a library of analogues. We aim to develop flow systems which will enable reactions to be performed on a synthetic useful scale.

The students will be the key beneficiaries of this research as they will be exposed to and be able to exploit a new form of
PhD training in the chemical sciences. In particular they will be able to input to and shape their project before embarking on
it - this will make a key impact on the science compared to the normal PhD route and will produce students who are
motivated and engaged from the start. Aspects of the course such as Brainstorming, regular problem sessions, Outreach
and Public Engagement, and the organization and delivery of the CDT-Syngenta Award to a world-leading academic will
produce students who are more confident in their own abilities. This in turn will have a real impact on their future careers
when making presentations or when interviewed, as well as fast tracking their leadership skills. Other aspects of the
training such as IP, Entrepreneurship and Commercialisation, will help stimulate and prepare these students for developing
their own Start-up ventures based around their science skills. Science and Technology SMEs are increasingly vital to the
UK's economy and if we are to make an impact on the world stage our next generation of scientists must be empowered to
move quickly and flexibly in that direction. At an academic level the science that these students will produce will make an
impact right across the chemical synthesis landscape and will train a new generation of academic unafraid to cross
chemical boundaries. These students promise to contribute to vitally important areas of society such as healthcare,
medicine, energy and food production - all requiring new molecular entities to be produced efficiently and effectively. The
nations health both financially (eg GDP) and physically (eg antibiotics) desperately need innovative new directions. For
example, the Pharmaceutical industry requires a new direction for drug discovery. One ripe area is to explore new 3D
molecular space, a space that just a few years ago would have been avoided due to complexity and expense. If new drug
IP is to be created, and tax revenue thereof, then we must train a new generation of molecule makers who are unafraid to
take on the challenges of this unexplored space and, more importantly, be able to exploit it commercially. We believe that
our Centre will be able to train PhD students with this level of scientific skill and commercial aspiration.
Our industrial stakeholders are invaluable to the the patronage and direction of the Centre and will benefit greatly from
direct interaction with the various cohorts during their tenure in the Centre. For example, by providing the CDT students
with industrial placements, an effective two way knowledge and skills exchange will operate: students will get invaluable
insight into small, medium and large industries; industry will see first hand the highly motivated and skilled students the
Centre produces as well as get access to much of the unique electronic teaching material that the Centre has developed.
Finally the CDT will have a positive impact on supervisor behavior by ensuring collaboration under conditions that are not
forced or artificial. All potential PhD projects submitted for Brainstorming must have at least two supervisors. This can be
either academic -academic (home/away) or academic-industrial. We have found with the current CDT that these proposals
must describe real collaborations or the students are unlikely to select them. This provides the right encouragement for
collaborators to generate strong proposals that will interest all parties, which in turn is leading to high quality publications in
high impact journals.