Details of Grant 

EPSRC Reference:	GR/S82480/01
Title:	Interavtive Michael Additions and the Total Synthesis of Lactonamycin
Principal Investigator:	Barrett, Professor T
Other Investigators:
Researcher Co-Investigators:
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Department:	Chemistry
Organisation:	Imperial College London
Scheme:	Standard Research (Pre-FEC)
Starts:	01 May 2004	Ends:	31 October 2007	Value (£):	214,432
EPSRC Research Topic Classifications:	Biological & Medicinal Chem. Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:	Pharmaceuticals and Biotechnology
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Panel History:
Summary on Grant Application Form
Lactonamycin is a natural product isolated from the culture broth of Streptomyces rishiriensis obtained from a soil sample collected near Yokohama City, Japan. Whilst it shows no activity against Gram-negative bacteria, it is significantly active against Gram-positive organisms. Moreover, it is especially effective against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. In addition, it showed appreciable levels of cytotoxicity against various tumour cell lines. On account of its superb biological activities and structural complexity, it is an excellent target for total synthesis both to further understand structure-activity relationships and to define the limits of synthetic methodology. The total synthesis of the antibiotic natural product lactonamycin will be undertaken. This will provide a flexible route for the elaboration of molecular sub-structures and analogues for bioassay. Additionally, the study will lead to the development of novel non-classical methods for glycosidation that use nitrosoalkene intermediates. The research will additionally highlight the versatility of the Michael reaction for the construction of delicate polyfunctional molecules. This work is relevant to the solution of a major biomedical need: the discovery of novel antibiotics effective against dangerous pathogenic organisms. As a result the research has potentially significant economic and social benefits.
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Organisation Website:	http://www.imperial.ac.uk