Transannular Macrocyclisation and the concise total synthesis of Antifungal natural products

Projektinformationen

POLYKETOMACROCYCLES

ID Finanzhilfevereinbarung: 7547

Startdatum 1 November 2005

Enddatum 31 Juli 2007

Finanziert unter

• 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

Gesamtkosten € 0,00

EU-Beitrag € 158 479,00

Koordiniert durch

IMPERIAL COLLEGE LONDON, DEPARTMENT OF CHEMISTRY
United Kingdom

Ziel

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.

Wissenschaftliches Gebiet

• medical and health sciences › basic medicine › medicinal chemistry
• natural sciences › chemical sciences › organic chemistry › hydrocarbons
• natural sciences › chemical sciences › organic chemistry › aromatic compounds

Schlüsselbegriffe

• Polyketide
• antifungal agents
• aromatisation
• catalysed acylation
• macrocyclisation
• metathesis
• natural products
• transannular reactions
• triketo-ester

Programm/Programme

• 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

Thema/Themen

• MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF)

Aufforderung zur Vorschlagseinreichung

FP6-2002-MOBILITY-5
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

EIF - Marie Curie actions-Intra-European Fellowships

Koordinator

IMPERIAL COLLEGE LONDON, DEPARTMENT OF CHEMISTRY

• EU-Beitrag: Keine Daten
• Adresse: South Kensington Campus ; LONDON ; Vereinigtes Königreich
• Gesamtkosten: Keine Daten