Radical Induced Ring Expansion of Tetramic Acids - Access to Anti-Fungal Agents

Stage IV Project - Reshma Patel

Supervisor Dr Russell Cox

Second Assessor Dr G. C. Lloyd-Jones

Background

2-Pyridones are a comparatively rare class of secondary metabolites. They are biologically formed by the condensation of a polyketide moiety and an amino acid or its derivative. Compounds such as funiculosin 1 possess interesting biological functions such as anti-fungal and anti-tumour properties. However functionalised 2-pyridones are extremely difficult to synthesise. 2-Pyridones may be biosynthesised via radical induced ring expansion of a tetramic acid 2, and this type of approach could be put to use chemically. Precedence exists for similar chemical reactions of carbocyclic molecules.



Programme

The synthesis of simple acyl tetramates bearing a hydroxyl functionality at the beta-carbon was achieved last year by Stephen Cone by reacting beta-hydroxy alpha-aminoesters 3 with acetone diketone adduct 4. The resulting beta-keto amides 5 were cyclised easily to form acyl tetramates 6. This project will focus on the generation of a radical next to the ring. This will be achieved by converting beta-alcohol 6 to a methyl xanthate 7. Tin Hydride reaction will deoxygenate and generate a radical at the required position. Characterisation of reaction products will be undertaken to determine whether the required ring expansion has occurred.

References

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. Cone, S. P. Final Year Project, University of Bristol 1997.
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. Barton, D. H. R.; Motherwell, W. B.; Stange, A. Synthesis, 1981, 743-745.