Project description
Advancing the synthesis of complex cyclic compounds for drug discovery
Inventing ways to form several bonds, stereocentres and rings in a single process is key to sustainable synthetic chemistry. By combining multicomponent reactions and tandem reactions into a single procedure, the diversity, complexity and value of products can be further enhanced. Researchers of the EU-funded CuTAN project will develop multicomponent coupling reactions of unsaturated hydrocarbons (allenes and enynes) with imines and boron reagents. Overall, the process will provide high-value cyclic (amine) products with high regio-, diastero- and enantiocontrol that possess a variety of synthetic handles. Molecular cyclic structures are commonly found in bioactive natural products and pharmaceutical molecules.
Objective
The invention of processes that can form several bonds, stereocentres and rings in a single process is key to a sustainable future in synthetic chemistry. Multicomponent reactions and tandem procedures are two strategies that enable the rapid build-up of molecular complexity from simple reagents. By combining these two strategies into a single procedure, the diversity, complexity and value of products can be further enhanced along with the efficiency and economy of their construction. In this project, Dr Satpathi will develop novel copper-catalyzed multicomponent couplings of unsaturated hydrocarbons (e.g. allenes, enynes) with imines and boron reagents. These procedures will provide high-value amine products with universally high regio-, diastero- and enantiocontrol. The products will bear a variety of synthetic handles, for example, amino, alkynyl/alkenyl, and boryl groups, thus the products are primed for subsequent transformation. Dr Satpathi will exploit this functionality in tandem intramolecular couplings (e.g. intramolecular Suzuki/Buchwald-Hartwig reactions) to provide core cyclic structures of drug molecules and natural products. Thus, through a tandem procedure of; 1) copper-catalyzed borofunctionalization, and; 2) subsequent transition-metal catalyzed cyclization, he will gain efficient access to highly sought-after complex molecules. Overall, the process will provide high-value, chiral, cyclic motifs from abundant, achiral, linear substrates. Finally, Dr Satpathi has identified the phthalide-isoquinoline family of alkaloids as target molecules to display the power of his tandem methodology. Dr Satpathi has devised a novel route, which begins with our tandem multifunctionalization/cyclization reaction, to provide a range of these important alkaloids. The chosen alkaloids are of particular interest as they display a range of bioactivities – for example as natural products, receptor antagonists and on-market drugs.
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Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
M13 9PL Manchester
United Kingdom