Many of Nature and apos;s most potent molecules have within their structure, a cyclic arrangement of atoms. Similarly, in the chemical industries, cyclic structural motifs are present in many products. In fact, cyclic organic molecules have an important role to play in all areas of life. The development of new ways to construct such molecules in a controlled and selective manner is understandably a key area of chemistry. We will build on recent discoveries from the Manchester group that show a single, acyclic starting material can be `directed down a number of different cyclization pathways by simply changing the alcohol co-solvent used in reactions with the popular reducing agent samarium iodide. These new, stereoselective cyclization reactions allow quick access to a range of molecular architectures found in targets of biological significance that are otherwise not easily made.
The project will involve work in several chemical disciplines including, organic synthesis, inorganic/organometallic chemistry, physical organic, and medicinal chemistry. The specific objectives are: - prepare N-heterocyclic frameworks by the cyclization of lactam substrates - assess the generality of the co-solvent `directing phenomenon - develop an asymmetric synthesis of new, cyclic a-amino acids - carry out a `directed, asymmetric synthesis of the core of the biologically active natural product, stolonidiol New organic reactions that allow drugs and other active agents to be constructed rapidly save time and other resources.
The principle of making many different products from a common starting material is also economically very attractive. In addition, the work will provide new building-blocks for use in biology and medicine, thus assisting the fight against disease and illness. The project will provide diverse, `tailored training for an excellent European researcher and will lead to scientific results that will enhance the profile of European research.
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