Cel The Barrett group has carried out extensive research on the synthesis of antifungal natural products and the underlying synthetic methodology with recent focus on targets such as nikkomycin B, papuamine, papulacandin, FR-900848, pramanicin, the palmarumyci ns and preussomerin G.This proposal concerns the total synthesis of two bioactive natural products zearalenone and 15G256b. These two macrocyclic compounds are respectively a mycotoxin and an antifungal agent. They possess a highly functionalised macrocycl ic core and 2,4-dihydroxybenzoic acid units, which are constituents of numerous macrocyclic bioactive natural products.The first objective of the research is the development of new and original strategies, which should allow concise access to these natural compounds. The first key step is the macrocyclisation reaction, which takes place by using an unusual metathesis reaction between an alkene and an alkyne, following an approach recently developed at Imperial College London. The second key step involves a transannular reaction to elaborate the arene entity fused to the macrocyclic ring by a biomimetic closure of triketo-ester moiety. The second objective of this work is the biological testing of the synthesised compounds by GlaxoSmithKline in the United Kingdom to evaluate their activities.This proposal describes a programme of interdisciplinary research. First, it is a synthetic chemistry because these polyfunctionalised compounds will be prepared by using original strategies and new methodologies. Secondly, it is also a medicinal chemistry because this route to zearalenone and 15G256b is also promising in that it could be applicable to others members of these classes of natural products and also allowing for the determination of structure-activity relationship with the antifungal agent 15G256b. The new synthetic methods should be of general interest for the preparation of diverse complex aromatic compounds of pharmaceutical importance. Dziedzina nauki medical and health sciencesbasic medicinemedicinal chemistrynatural scienceschemical sciencesorganic chemistryhydrocarbonsnatural scienceschemical sciencesorganic chemistryaromatic compounds Słowa kluczowe Polyketide antifungal agents aromatisation catalysed acylation macrocyclisation metathesis natural products transannular reactions triketo-ester Program(-y) 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 Temat(-y) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Zaproszenie do składania wniosków FP6-2002-MOBILITY-5 Zobacz inne projekty w ramach tego zaproszenia System finansowania EIF - Marie Curie actions-Intra-European Fellowships Koordynator IMPERIAL COLLEGE LONDON, DEPARTMENT OF CHEMISTRY Wkład UE Brak danych Adres South Kensington Campus LONDON Zjednoczone Królestwo Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych
