Palladium catalyzed C(sp3)‒H late-stage diversification of biologically active molecules

Información del proyecto

LATE-STAGE

Identificador del acuerdo de subvención: 702462

DOI

10.3030/702462

Proyecto cerrado

Fecha de la firma de la CE 24 Febrero 2016

Fecha de inicio 1 Marzo 2016

Fecha de finalización 28 Febrero 2018

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 183 454,80

Aportación de la UE

€ 183 454,80

Coordinado por

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom

Objetivo

Aliphatic amines are central to the function of many biologically active molecules as evidenced by their prevalence in a large number of pharmaceutical agents. The groups appended to these nitrogen atoms are crucial in determining the physical properties of the amine and are linked to how well it interacts with a biological target. Despite the apparent simplicity of the aliphatic amine motif, the number of general methods that allow their late-stage functionalization directly on the bioactive compound is surprisingly limited, and so the development of directed catalytic methods remains an important challenge. Metal catalysed C–H activation represents a versatile tool for late-stage functionalization. It mostly relies on directing functional groups to functionalize C–H bonds. Recently, Professor Gaunt at the University of Cambridge has uncovered a new C–H activation mode that enables the conversion of hindered amines into β-lactams and aziridines. The first objective of this proposal aims to directly apply the transformations developed by Gaunt, e.g. carbonylation, aziridination and acetoxylation reactions, to a precise class of drugs that contain the secondary amine motif as central function, i.e. β-adrenergic drugs. The use of the oxidative Pd(II)/(IV) catalytic cycle will then allow the development of a novel fluorination. The second objective relies on a new methodological concept, which seeks to merge palladium catalysis with radical chemistry, opening a route to develop novel perfluoroalkylation, amination and methylation reactions via a new Pd (II)/(III)/(IV) catalytic cycle. Finally, the third aim will be to apply all the methods developed to four important anticancer drugs, in collaboration with the new AstraZeneca oncology unit in Cambridge, to prepare novel analogues for biological testing.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias químicas › química inorgánica › compuestos inorgánicos
• ciencias naturales › ciencias químicas › química inorgánica › metales de transición
• ciencias naturales › ciencias químicas › química orgánica › alcoholes
• ciencias naturales › ciencias químicas › catálisis
• ciencias naturales › ciencias químicas › química orgánica › aminas

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions PROGRAMA PRINCIPAL
  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
  

Tema(s)

• MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF)
  

Régimen de financiación

MSCA-IF-EF-ST - Standard EF

Convocatoria de propuestas

H2020-MSCA-IF-2015

Coordinador

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

• Aportación neta de la UEn: € 183 454,80
• Dirección: TRINITY LANE THE OLD SCHOOLS ; CB2 1TN CAMBRIDGE ; Reino Unido
• Región: East of England › East Anglia › Cambridgeshire CC
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: € 183 454,80