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Electrophilic Indoles for the Enantioselective Synthesis of Benzofuroindolines related to Diazonamide A

Objective

The objectives of this project are the development of A new and efficient asymmetric oxidative coupling reaction between phenols and indoles for the synthesis of benzofuroindolines analogs of diazonamide A and the biological evaluation of a library of this family of compounds.
The benzofuroindoline core is a unique motif found in the natural products diazonamide A, a very potent anti-cancer agent (<5 nM against various cell lines) which may have clinical utility for cancer therapy since it is as active as widespread used antimitotic drugs without their overt toxicity. Unfortunately, the known synthetic methods for the generation of the benzofuroindoline scaffold are not short, high yielding and enantioselective at the same time. Therefore, we aim to study and develop direct and general methods for the synthesis of this important pharmacophore. We desire to use as starting materials phenols and indoles that are the postulated biosynthetic precursors of the natural benzofuroindolines.
To meet this goal, we propose an innovative strategy based on the scarsely known electrophilic character of the indole nucleus.
We will particularly aim at the development of enantioselective catalytic reactions.
After the development of suitable reactions for the synthesis of benzofuroindolines, we intend to create a library of analogs of diazonamide A that will be evaluated against different tumoral cell lines in order to discover simplified analogs which would be synthesized in few steps with retention of the clinical potential of diazonamide A.
The research will be conducted at the Institut de Chimie Moléculaire et des Matériaux d’Orsay (ICMMO), Université Paris-Sud 11 by Raj Kumar Nandi under the responsability of Guillaume Vincent.

Call for proposal

FP7-PEOPLE-2013-IIF
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Coordinator

UNIVERSITE PARIS-SUD
Address
Rue Georges Clemenceau 15
91405 Orsay Cedex
France
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 194 046,60
Administrative Contact
Nicolas Lecompte (Mr.)