Details of Grant 

EPSRC Reference:	GR/L41646/01
Title:	SYNTHESIS OF SPONGISTATIN 1 (ALTOHYRTIN 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 October 1997	Ends:	28 February 2001	Value (£):	198,134
EPSRC Research Topic Classifications:	Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:	No relevance to Underpinning Sectors
Related Grants:
Panel History:
Summary on Grant Application Form
The spongistatins (aka altohyrtins), isolated in microscopic quantities from marine sponges (ca 10-7% yield), show especially powerful growth inhibitory activity against human melanoma, lung, colon and brain cancers. They have an activity pattern similar to the microtubule-interactive antimitotics and are believed to function by inhibiting tubulin polymerisation. Realisation of a total synthesis of spongistatin 1 will satisfy the urgent need for further material for biological testing, as well as enabling the determination of the full relative and absolute stereochemistry. The project plans to achieve a viable, convergent synthesis based mostly on the application of boron reagents for the stereocontrolled construction and coupling of smaller fragments. The synthetic route is designed with sufficient flexibility to subsequently provide a diverse range of structural analogues of the spongistatins for SAR studies. This project will also stimulate the development of new and practical methods for the stereocontrolled synthesis of the polyketide class of bioactive polyoxygenated natural products. In particular, remote (1, 5-) asymmetric induction will be explored in the aldol reactions of a range of chiral methyl ketones, which should allow a general entry into 1, 3-polyol construction and polyacetate-derived structures.
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Organisation Website:	http://www.cam.ac.uk