Details of Grant 

EPSRC Reference:	GR/R97245/01
Title:	The Manzamine Alkaloids: Synthesis and Biological Evaluation
Principal Investigator:	Coldham, Professor I
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	Chemistry
Organisation:	University of Exeter
Scheme:	Standard Research (Pre-FEC)
Starts:	06 April 2003	Ends:	31 July 2003	Value (£):	116,351
EPSRC Research Topic Classifications:	Biological & Medicinal Chem. Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:	Pharmaceuticals and Biotechnology No relevance to Underpinning Sectors
Related Grants:
Panel History:	Panel Date Panel Name Outcome 22 May 2002 Chemistry prioritisation panel May 2002 Deferred
Summary on Grant Application Form
This proposal outlines research in synthetic organic chemistry, centred on the synthesis of the natural product manzamine A, which has been shown to have significant anticancer and antimalarial activity. We have developed a highly efficient and stereoselective route to the manzamine alkaloids using dipolar cycloaddition chemistry and have prepared four of the five rings of manzamine A. The aim of this research is to complete the synthesis, making use of our cycloaddition chemistry. The main objective is to elaborate the ABCE ring system that we have prepared, by introducing the required (3-carboline unit and then forming the final ring D, hence completing the synthesis of this complex polycyclic alkaloid. The p-carboline unit could be introduced in a number of ways, one of which involves a Heck reaction and new methodology towards the formation of Heck addition products from aryl halides or triflates and unsaturated ketones will be studied. The compounds prepared during the synthesis of the natural product, and analogues prepared as a result of the coupling reactions, will be submitted for biological tests. Information on the role and importance of the aromatic and other functional groups in the molecule will be probed.
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Organisation Website:	http://www.ex.ac.uk