Descripción del proyecto
Mejorar la síntesis de compuestos cíclicos complejos para el descubrimiento de fármacos
Concebir métodos para crear varios enlaces, estereocentros y anillos en un solo proceso es esencial para el sector de la química sintética sostenible. La diversidad, la complejidad y el valor de los productos pueden mejorarse aún más al combinar reacciones multicomponente y reacciones en tándem en un solo procedimiento. Los investigadores del proyecto CuTAN, financiado con fondos europeos, diseñarán reacciones multicomponente de acoplamiento de hidrocarburos insaturados (alenos y eninos) con iminas y reactivos del boro. En general, el proceso rendirá productos cíclicos (aminas) de alto valor con una elevada enantioselectividad, diastereoselectividad y regioselectividad y que poseen una variedad de grupos de unión sintéticos. Estas estructuras cíclicas moleculares son comunes en productos bioactivos naturales y en moléculas farmacéuticas.
Objetivo
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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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
M13 9PL Manchester
Reino Unido