Details of Grant 

EPSRC Reference:	EP/D501725/1
Title:	New Asymmetric Reactions and their Application in Total Synthesis
Principal Investigator:	Aggarwal, Professor VK
Other Investigators:	Harvey, Professor J Lindsay, Dr DM
Researcher Co-Investigators:
Project Partners:	AstraZeneca GlaxoSmithKline plc (GSK)
Department:	Chemistry
Organisation:	University of Bristol
Scheme:	Standard Research (Pre-FEC)
Starts:	01 October 2005	Ends:	28 February 2011	Value (£):	1,489,921
EPSRC Research Topic Classifications:	Biological & Medicinal Chem. Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:	Chemicals Pharmaceuticals and Biotechnology
Related Grants:
Panel History:
Summary on Grant Application Form
Many important molecules required for life exist in two forms that are mirror images of each other. They are related like our left and right hands, but they are not the same. This property is called chirality, from the Greek word for hand, and the two forms are called enantiomers, from the Greek word for opposite. Perhaps surprisingly, Nature mainly uses only one of the two enantiomers available. Many drugs consist of chiral molecules and in the past a mixture of the two enantiomers was routinely employed since it is much easier to produce than the single more effective enantiomer. Since the catastrophic case of thalidomide, this scenario has changed and now two enantiomers of a chiral compound have to be treated as different products and are required to be tested separately. Consequently, it is vital to be able to produce the two chiral forms separately, particularly because they cannot easily be separated from a mixture. It is within this setting that organic synthesis has evolved in the last few decades.In a synthesis starting molecules are used to build new molecules by means of various chemical reactions. Organic synthesis generally involves the reaction between two molecules - a nucleophile and an electrophile. These are attracted to each other - rather like opposite poles of a magnet - and a chemical bond is created between them. One class of useful nucleophiles are organometallic reagents as they readily react with electrophiles to make new bonds. However, chiral organometallic reagents are very rare, but clearly if they could be easily prepared they would be extremely useful as they would provide a direct synthesis of a broad range of chiral molecules. We propose a unique method for generating configurationally stable chiral organometallics and then we will explore what classes of electrophiles they react with. With this information we will then apply the new chemistry in the synthesis of biologically important molecules that are otherwise difficult to make. This will particularly highlight the power of the new methodology.Finally, if the nucleophile and electrophile are composed of almost equal halves of a complex molecule then a more efficient synthesis is achieved (convergent synthesis) compared to building up the molecule piece by piece (linear synthesis). We have developed a very useful class of chiral nucleophiles (sulfur ylides) and now wish to exploit their use in highly convergent syntheses of complex molecules.A range of methodologies and their applications in synthesis are proposed in this proposal with common themes of synthesis and chirality. They are all linked together in that each methodology involves a nucleophile bearing a group that makes it behave as a nucleophiles but also leaves during the course of the reaction. We believe that reactions of this class of nucleophiles with conventional and non- conventional electrophiles will open up a whole new area of synthesis.
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Organisation Website:	http://www.bris.ac.uk