Details of Grant 

EPSRC Reference:	EP/E052185/1
Title:	General and Convergent Strategy for Asymmetric Synthesis
Principal Investigator:	Aggarwal, Professor VK
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	Chemistry
Organisation:	University of Bristol
Scheme:	Senior Fellowship
Starts:	01 October 2007	Ends:	31 March 2013	Value (£):	984,771
EPSRC Research Topic Classifications:	Biological & Medicinal Chem. Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:	Chemicals Pharmaceuticals and Biotechnology
Related Grants:
Panel History:	Panel Date Panel Name Outcome 22 Mar 2007 Chemistry Fellowships Sift Panel 2007 FinalDecisionYetToBeMade 24 May 2007 Fellowships Central Allocation Panel 2007 InvitedForInterview
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. Thus, there is a strong industrial need fuelled by the pharma and agrochemical industries to be able to produce single enantiomers for testing and ultimately marketing. These large industries clearly impact on our every day lives: we need to eat, and need help to fight off disease. But chirality also has a major impact in biology. Anyone studying biological processes needs to make small molecules with the correct chirality to interact appropriately with the natural host. Chirality is also important in materials. The properties of polymers and liquid crystals are directly related to how they align (conformation) and stereogenic centres along the polymer chain can force the chain to turn right/left or go straight on (depending on whether it is a right or left handed centre). Thus, from medicine to materials, chirality is important. It spans all the scientific disciplines because it is a fundamental property of matter. Clearly, chemical processes that create chirality are extremely important. Chemical processes (synthesis) that create new C-C bonds from simpler molecules are also hugely important as this is how chemical complexity is built up. 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.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 and provide a step change in asymmetric synthesis that could have far reaching consequences.
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