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Development of a novel tandem ring closing metathesis process as a general route to the first syntheses of various lycorine type alkaloids

Objective

Cancer is the leading cause of death worldwide and therefore a continued need exists for new drugs with new modes of action. To date, over 60% of drugs employed to target cancer are natural product derived or inspired and this places significant importance on research into the total synthesis of natural products. It also supports the need for the “next generation” of researchers to receive training in this area in order to enable the EU to remain globally competitive. The lycorine family of natural products have shown promise for the development of novel drugs; however a full study requires general access to these alkaloids. We propose a research project to develop methodology for the first syntheses of these complex natural products and novel derivatives, in order to enable future biological testing.
For an efficient synthesis of these compounds, we envisage the development of a novel tandem RCM sequence, which can afford, in a single event, a decorated tetrahydroindole skeleton bearing an enol ether, which is crucial to the post-functionalisation of the bicycle. This methodology would allow a straightforward and selective synthesis of numerous lycorine alkaloids not synthesised to date. We also propose to explore the benefits of using Flow Chemistry, in particular to extend the methodology to more sensitive substrates. This is a rapidly expanding and exciting area of research, and dissemination of this knowledge within Europe in the near future is important. This proposal also offers the opportunity to establish future collaborations in this area, strengthening EU competitiveness.
The applicant is an outstanding British female scientist and this fellowship would facilitate her pursuit of an independent academic career within the EU and her ability to become a future role model for women in science.

Field of science

  • /medical and health sciences/clinical medicine/cancer

Call for proposal

FP7-PEOPLE-2011-IEF
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

UNIVERSITE JOSEPH FOURIER GRENOBLE 1
Address
Avenue Centrale, Domaine Universitaire 621
38041 Grenoble
France
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 193 594,80
Administrative Contact
Yann Le Roux (Mr.)