Objective The research program will focus on the total synthesis of the miharamycins, the development of synthetic approaches allowing access to these nucleoside antibiotics and a range of analogues, for biological testing purposes.The miharamycins possess combined structural features of monosaccharides, nucleosides and peptides. Potent biological activity of nucleoside antibiotics has provoked a large amount of synthetic interest.However the miharamycins themselves have not yet been synthesised and the absolute stereochemistry at one chiral centre is as yet unknown. The miharamycins are potent inhibitors of Pyricularia oryzae, which produces rice blast, and as such are important targets for the improvement of food production.The synthetic studies will consist of three phases: the development of a new approach to the synthesis of the central carbohydrate portion by the use of a ring closing metathesis reaction; the development of methodology for a one carbon extension at C-6 and attachment of the amino acid portion; and finally glycosylation with a purine base to complete the total synthesis.In addition to the total synthesis, a variety of structural analogues will be accessed in a parallel fashion as follows: variation of carbohydrate stereochemistry; variation of amino acid for coupling to C-6; variation of purine / pyrimidine base for installation at the anomeric centre.These studies will provide the first total synthesis of miharamycin and thereby provide structural confirmation of the stereochemistry of the natural product at C-6. They will also produce an extremely interesting set of analogous materials for biological testing which will enable the deduction of structure activity relationships.These studies will also entail the development of novel synthetic methodology that will find use more generally in the wider context of nucleoside synthesis, which will be of extreme importance for the development of the next generation of anti-virals and antibiotics. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculescarbohydratesmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsnatural scienceschemical sciencesorganic chemistryaminesmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Call for proposal FP6-2002-MOBILITY-5 See other projects for this call Funding Scheme EIF - Marie Curie actions-Intra-European Fellowships Coordinator CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Address University offices, wellington square Oxford United Kingdom See on map Links Website Opens in new window EU contribution € 0,00
