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Details of Grant 

EPSRC Reference: EP/E033261/1
Title: Total synthesis of the guanacastepenes
Principal Investigator: Greaney, Professor M
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Sch of Chemistry
Organisation: University of Edinburgh
Scheme: Standard Research
Starts: 10 September 2007 Ends: 09 September 2010 Value (£): 119,261
EPSRC Research Topic Classifications:
Biological & Medicinal Chem.
EPSRC Industrial Sector Classifications:
Chemicals Pharmaceuticals and Biotechnology
Related Grants:
Panel History:  
Summary on Grant Application Form
Molecules come in all shapes and sizes, and new ways of making them are central to just about every industry in the twenty-first century. Medicine, manufacturing, cosmetics and agriculture are just a few important examples of industries that depend on chemists coming up with new molecules and new methods for putting them together. The current proposal is looking to make one of nature's molecules, called guanacastepene, a natural product that is found in tropical mushrooms. The construction of a natural product by chemists in a laboratory is a challenging endeavour, as the structure of these molecules is often very complex. As a result, chemistry of the highest quality is needed. We are trying to invent new chemical reactions that are designed to be especially powerful for making complicated structures like natural products. The use of nature's molecules to inspire bigger and better chemistry is a hallmark of this branch of science; many of the chemical reactions now taken for granted and used all over the world arose from research programmes in natural product chemistry. Just as the synthesis of natural products have inspired advances in the chemical sciences, they are responsible for huge innovations in biology and medicine. The use of plants and herbs as natural remedies has been documented since the beginning of recorded history. What is arguably less well-known is that this process continues to this day within the laboratories of the pharmaceutical industry. Estimates have put the percentage of modern medicines that derive from natural products as high as 50%. The natural products can be used directly, such as aspirin or penicillin; modified slightly by chemists to produce medicines (e.g. the cholesterol lowering drug Mevacor) or modified more substantially such that the natural product represents a kind of starting point. In the current proposal, the natural product guanacastepene has powerful biological activity against the virulent pathogen MRSA, the number one target for the development of new antibacterial drugs. However, it is far too toxic to stand as a drug in its own right, and falls into the category alluded to above as one of nature's molecules that needs to be chemically modified before its potential as a medicine can be harnessed. In synthesising this molecule in the laboratory, we aim to develop the chemistry necessary for modification of guanacastepene such that it loses its toxicity but retains its antibacterial activity, opening the door to explore its potential as a new drug for the treatment of infection.
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