SNSF | P3 Research Database

organic synthesis; asymmetric synthesis; chiral relay radical reactions; non-toxic reagents; environmentally friendly processes; biologically active compounds; radical reactions; organometallic reagents; alkaloids; natural products; chiral catalysts

English title	Synthetic Methods for total Synthesis of Natural Products
Applicant	Renaud Philippe
Number	119998
Funding scheme	Project funding (Div. I-III)
Research institution	Departement für Chemie und Biochemie Universität Bern
Institution of higher education	University of Berne - BE
Main discipline	Organic Chemistry
Start/End	01.04.2008 - 31.03.2011
Approved amount	1'050'630.00

Lead

Lay summary
The total synthesis of natural products and analogues proved over the years to be the most reliable method for the discovery of new drugs. Due the structural complexity of many natural products, efficient synthetic methods are required to synthesize them. Our research program aims at finding methods and strategies that can be applied for efficient synthesis of different classes of products possessing an interesting biological profile. Development of processes involving radical chemistry, organometallic chemistry and enantioselective catalysis will be investigated. Our research focus on increasing the efficiency of target molecule synthesis by minimizing the number of synthetic steps, by opening new synthetic pathways, and by developing environmentally friendly reagents. The project is subdivided in six sub-chapters according to synthetic methods: Boron reagents for radical chemistry. Our effort will be concentrated on the development of non-toxic and environmentally friendly reagents to perform efficient radical reactions. Organoboranes will be used as radical precursors and as reagents to replace toxic tin derivative for a wide range of radical reactions. Activation of water and alcohols by boron derivatives. Replacing toxic reagent such as metal hydrides (in particular tin hydride) by water and alcohols for the reduction of radicals is a particularly promising research field to expend the utility of radical reactions. Radical translocation-cyclization processes. Selective activation of an unreactive position of an organic molecule without using any transition metal can be accomplished via radical 1,5-hydrogen transfer. Extension of this chemistry to cascade reactions will shorten dramatically the length of some natural product syntheses. Radical Azidation. The formation of carbon-nitrogen bonds under very mild reaction conditions represents a very useful tool for the total synthesis of alkaloids. Efficient reagents to achieve such a transformation are under development. Annulation reactions via carbometallation of non activated alkynes. This project is directed towards the preparation of moderately complex chiral building blocks for the synthesis of biologically relevant products. A novel annulation procedure will be developed that should afford 5-membered rings via a domino reaction. Preparation of N-heterocyclic compounds. In this part, an efficient functionalization of lactams will be used to prepare advanced building block for alkaloid synthesis. Desymmetrization of spirocyclic lactams will be examined in order to prepare to optically pure alkaloids. Application of this chemistry for the preparation of Cephalotaxus alkaloids, a class of very potent anticancer agents, will be developed.