Description du projet :
Carbonyl ylides are interesting organic intermediates that are harnessed for the synthesis of numerous heterocycles and related natural products via cycloaddition reactions. Hitherto they are generated via numerous procedures that involved organic solvents, metal catalysts, bases, additives and in general required more than mild reaction conditions. Herein we propose to develop an ecofriendly synthetic strategy for the generation of carbonyl ylides and then apply them in situ for a cycloaddition reaction with substituted maleimides as appropriate dipolariphiles for the generation of 4, 6-dioxo-hexahydro-1H-furo[3, 4-c] pyrrole. These are novel building blocks and our proof of concept molecular modelling studies have indicated them to be potential anicancer compounds acting as poly ADP ribose polymerase (PARP) inhibitor. PARP inhibitors (PARPi) were shown to be effective against BRCA-deficient cancers and was subsequently approved as a therapy. Although effective, high cost and rapid onset of resistance necessitates the need to develop alternative therapeutic approaches in addition to the PARPi-based therapies. Our objectives will be to identify a suitable environmentally sustainable photochemical stratgey to generate carbonyl ylides and then facilitate a [3+2] cycloaddition reaction in situ to afford the desired compounds. We intend to use variety of LED source viz. white, green, blue and red at various intensities in presence of numerous ecofriendly solvents like water, isopropanol, 2-methyl tetrahydrofuranetc. We do not intend to use any bases, catalysts and additives so as to make the procedure as « green » as possible. We also intend to develop a chromatography free isolation technique, preferably by crystallisation or precipitation of the final product from the reaction mixture. We aim to generate a library of ~50 compounds with diverse substitutions. We finally intend to perform functional analysis of these potential PARPi through in vitro PARylation assay and also against various cancer cells to assess their anticancer activity.
Research team within HES-SO:
Gremaud Ludovic
Durée du projet:
01.12.2023
Montant global du projet: 35'000 CHF
Archivage des données:
Leading House South Asia and Iran
Statut: Ongoing
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