Details of Grant 

EPSRC Reference:	EP/C541677/1
Title:	Synthesis and Stereochemical Determination of Spirastrellolide A
Principal Investigator:	Paterson, Professor I
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	Chemistry
Organisation:	University of Cambridge
Scheme:	Standard Research (Pre-FEC)
Starts:	01 May 2005	Ends:	30 April 2008	Value (£):	286,893
EPSRC Research Topic Classifications:	Biological & Medicinal Chem. Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:	Healthcare Pharmaceuticals and Biotechnology
Related Grants:
Panel History:
Summary on Grant Application Form
Marine organisms, particularly sponge invertebrates, are a prolific source of novel biologically active compounds with unusual, and often complex, structures. The harsh environment in which marine sponges inhabit, together with their lack of physical defences, requires that these organisms develop chemical deterrents for defence and survival. As a result, many of their associated organic compounds exhibit exceptional levels of biological activity, often combined with unique modes of action. However, the pre-clinical and clinical development of marine-derived natural products is often hampered by the limited supply - making total synthesis of vital importance. Not only does total synthesis enable the unambiguous structural determination of new natural products but it allows for the production of novel analogues, which may have more desirable therapeutic properties and greater accessibility. This project is to pursue the synthesis and structure dermination of spirastrellolide A, a complex polketide natural product isolated in 2003 from a Caribbean marine sponge. Spirastrellolide represents an entirely new structural type as a potent antimitotic agent, and preliminary biological studies indicate that it acts as a specific inhibitor of protein phosphatase 2A and causes premature cell entry into mitosis, which may have chemotherapeutic utility. However, there is a supply issue and, furthermore, the full structure of spirastrellolide is presently unknown, making the chemical synthesis an even more adventurous undertaking.
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Organisation Website:	http://www.cam.ac.uk