Objective In the frame of this research program, carried out at the Institute of Molecular Sciences (ISM) at the University of Bordeaux (UB), we propose a strategy directed towards the first total synthesis of leucophyllidine, a cytotoxic alkaloid recently isolated from L. griffithii. From the retrosynthetic analysis of the target, two fragments where identified that will be prepared then connected in the last stage of the synthesis, following a biomimetic approach. The “North-fragment” will be synthesized relying on a coupling between a key-aldehyde moiety and tryptamine through a Pictet-Spengler reaction/lactamization cascade. The “South-fragment” will be elaborated using a Friedländer-type condensation between a piperidinone, and an ortho-aminobenzonitrile. The key-aldehyde and the piperidinone will be elaborated using a unified strategy, including a novel stereoselective free-radical carbo-oximation process, which will install quaternary centers present in North and South fragments. Incorporation of the vinyl motif on the naphthyridine ring, through a Suzuki coupling, should complete the synthesis of the south-fragment. Both fragments will finally be connected, following a biomimetic Mannich-type strategy, which should provide sufficient quantities of this potent anticancer agent and analogues for future biological screening. Key objectives of this research program are the development of an access to new plant anticancer drugs for potential clinical use and the training of future leading experts in the field of natural product–derived drugs discovery, a domain in which Europe must remain competitive in the 21st century as cancer-related diseases are rapidly increasing with population’s life expectancy. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural scienceschemical sciencescatalysisphotocatalysisnatural scienceschemical sciencesinorganic chemistrypost-transition metalsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancenatural sciencesbiological scienceszoologymammalogy Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator UNIVERSITE DE BORDEAUX Net EU contribution € 185 076,00 Address PLACE PEY BERLAND 35 33000 Bordeaux France See on map Region Nouvelle-Aquitaine Aquitaine Gironde Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 185 076,00
