Research in the Cook group spans three main areas which include:
- The development of new enantioselective palladium catalyzed cascade rearrangement reactions.
- The use of Lewis acid and hydrogen-bond donor catalysts to promote new cascade sigmatropic rearrangements.
- Design, synthesis and evalution of novel JNK inhibitors for the development of new anti-inflammatory therapeutics.
The aims of both areas 1 and 2 (above) are developing new cascade rearrangements for the synthesis of challenging stereodefined molecules. Although they utilize very different chemistry, with one using transition metal catalysis and the other organocatalysis, they have the same overarching principle of harnessing the power of cascade rearrangement chemistry. The advantages of cascade reactions over linear syntheses is highlighted below.
Linear Approach to Synthesis
- The synthesis of complex organic molecules, such as pharmaceuticals, require multi-step reaction sequences.
- Each step requires different reagents and purifications making them time, step and atom-inefficient processes.
Cascade Approach to Synthesis
- Nature synthesizes complex molecules through cascade reactions using enzymes as catalysts with impressive levels of selectivity.
- Inspired by nature, we are developing several cascade reactions which use a single unified set of conditions allowing us to access and utilize unstable intermediates.
- We have developed several reactions that can perform up to three-steps with a single catalyst.
- Carefully designed cascade minimize time, cost and waste, while increasing yields and selectivity.
Medicinal Chemistry – Novel JNK-Inhibitors
Our other area of focus is the development of novel JNK-inhibitors for the treatment of severe inflammatory diseases and conditions. This research is in collaboration with Prof. Mark Quinn (MSU Microbiology and Immunology) and aims to develop new and selective inhibitors against all three isoforms of these proteins (JNK-1/2/3). c-Jun-N-Terminal Kinase (JNK) proteins have been demonstrated to be a major factor in inflammatory conditions, ranging from autoimmune diseases, such as rheumatoid arthritis, to stroke. Our aim is to design, synthesize and explore the structure activity relationship (SAR) of these proteins to develop potent and selectivity inhibitors of each isoform. Selectively inhibiting each of the JNK-1/2/3 proteins will potentially provide pathways to develop therapeutics for a range of different indication.