Objectif The search for new drugs and antibiotics remains a very important activity. In this context, peptides continue to play a central role. There are many examples of biologically active peptides, including examples of cyclic and cyclic structures. Unlike their cyclic congeners, cyclic peptides exhibit substantial resistance to proteoloyticenzymes, and can exhibit both irreversible and reversible inhibition of such enzymes, and for this reason they are potential drugs. Some examples of natural products falling into this class include the angiotensin converting enzyme inhibitor K-13 and the amino peptidase inhibitor OF4949-III. There is therefore substantial interest in the preparation of analogues of these compounds as potential therapeutic agents. The Host group has recently completed the shortest synthesis of K-13 so far reported. This new route relies on the preparation of a highly functionalised tripe tide organizing reagent, which can be prepared efficiently from simple starting materials, and which can then be converted using palladium catalysis into the cyclic peptide. With this precedent, the objective of this project is to develop synthetic routes to the naturally occurring antibiotic biphenomycin B and the recently discovered protease inhibitors of the TMC-95 class, which are also macro cyclic peptides, together with less oxidised analogues of TMC-95. It is planned to use a similar strategy, involving the intermolecular coupling of highly functionalised organizing reagents with aryl iodides, catalysed by palladium (0). The benefit of this route is that it minimises the use of protection and deprotectionsteps, thus ensuring an efficient synthesis. The use of peptide derivatives containing two carbon-zinc bonds will also be explored, since this would allow Avery fast synthesis of biphenomycin B. Reagents such as this have never been previously prepared, and this represents a substantial element of novelty. Champ scientifique natural sciencesbiological sciencesmicrobiologybacteriologynatural scienceschemical sciencesinorganic chemistrytransition metalsnatural sciencesbiological sciencesmicrobiologymycologynatural sciencesbiological scienceszoologyentomologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Mots‑clés Amino acids organozinc reagents palladium peptides 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 Thème(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Appel à propositions FP6-2002-MOBILITY-5 Voir d’autres projets de cet appel Régime de financement EIF - Marie Curie actions-Intra-European Fellowships Coordinateur UNIVERSITY OF SHEFFIELD Contribution de l’UE Aucune donnée Adresse Western Bank, firth court SHEFFIELD Royaume-Uni Voir sur la carte Coût total Aucune donnée