Research
Organocatalysis
The development of small metal-free molecules capable of catalysing chemical reaction is (in our opinion) one of the most challenging and rewarding fields in contemporary organic chemistry.
- Green Chemistry: biodegradable, recyclable aprotic Brønsted acids
- Nanoparticle supported catalysts
- Nucleophilic asymmetric catalysis
- Sulfide-based catalysts for enantioselective epoxidation
- Enzyme mimics
New synthetic methodology
We are interested in the development of new organocatalytic reactions and processes of high synthetic utility. Representative examples of recent projects are shown below.
- Selective intermolecular crossed Tishchenko reactions
- Tandem catalysis: thiol kinetic resolution coupled with anhydride desymmetrisation
- Bishydroalkoxylation of alkynes a one pot natural product synthesis
Medicinal chemistry: anti-cancer drug design
Paullones are tetracyclic indole-based compounds that have been demonstrated to act as powerful cyclin-dependent kinase (CDK) inhibitors with potential anti-tumour properties. These relatively new drug candidates have yet to be fully developed as targets for anti-cancer drug design. We (in collaboration with Prof. D. H. Grayson) are engaged in the design of a range of paullone derivatives, with the dual aim of both maximising CDK1 binding selectivity and in vivo activity. A study to evaluate the inhibitory activity of these compounds against a range of kinases identified 9-azapuallone N-oxide as a selective inhibitor of CDK9/cyclin T. The potential significance of the function of CDK9/cyclin T in a range of medicinally relevant domains such as cell cycle/transcription regulation, HIV-1 replication and cardiovascular disease is only beginning to be understood, thus the development of highly selective inhibitors of this complex is a goal of considerable interest.