Integrated catalysis opens new arylation pathways via regiodivergent enzymatic C–H activation
Journal: Nature Communications
Publication Date: 30 August, 2016
Department of: Chemistry
One-pot integrated catalysis opens up new horizons in enzyme chemistry
Researchers at the University of Manchester have developed methods whereby enzymes and synthetic metallo-catalysts can be brought together in tandem to catalyse reactions that were previously inaccessible using existing methods.
The team used halogenase enzymes to introduce halogen substituents into selected positions of aromatic compounds typically found in drug molecules. A synthetic palladium catalyst then exchanges the halogen for a variety of other substituents, creating a wide range of new structures that would be difficult to access using conventional means. To overcome the issue of catalyst incompatibility, a special membrane was used to separate the two catalytic systems. Whilst the catalysts cannot penetrate the membrane, other components of the reaction, including the halogenated intermediates, can pass through from the enzyme to the palladium catalyst.
It is envisaged that the integrated catalysis approach could open the way to more elaborate cascade reactions, with simple starting molecules passing through membranes from one catalyst to the next, to rapidly deliver complex products with no need to isolate any reaction intermediates.
- An enzyme is a protein evolved in nature to catalyse metabolic reactions. In this research halogenase enzymes from bacteria and fungi are used to introduce halogens (chlorine or bromine) into organic molecules.
- The synthetic (non-natural) palladium containing catalysts used in this study couples the halogen containing molecules with other activated molecules leading to more complex structures.
- Integrated catalysis involves combining multiple different catalysts in a single process allowing complex molecules, like pharmaceuticals, to be produced more efficiently with less waste.