Research Fellows Directory
Professor Nigel Simpkins
University of Birmingham
Our current and future research is focused on the area of asymmetric organocatalysis using chiral Bronsted bases, particularly for the asymmetric synthesis of amino acids, diketopiperazines (DKPs), and related compounds. We have established that triketopiperazines (TKPs) are especially useful as substrates for asymmetric organocatalysis, allowing the formation of masked quaternary amino acids and their derivatives, and also enabling rapid access to polycyclic structures resembling bioactive natural products.
These types of molecules are potentially extremely useful in drug discovery to achieve optimal medicinal chemistry properties in the pharmaceutical industry. There is a growing recognition that molecular complexity and chirality play an important role in achieving in-vivo activity and selectivity. Industry has recognised that these properties can play a key part in avoiding costly late-stage clinical candidate attrition, and has acknowledged the need to escape ''flat land'' and embrace (chiral) sp3-rich lead compounds. Many commercial compounds are not suitable for screening. Also, compounds active against pathogens appear to accupy physicochemical space not well addressed by traditional pharma screening libraries. Linked to this is a growing appreciation that diversity-orientated synthesis, incorporating motifs prevalent in bioactive natural products, is a powerful discovery strategy.
The capability to use catalytic asymmetric chemistry to make more sophisticated ‘effect molecules’ in a resource-efficient way is likewise extremely important. We hope to make contributions to this area with our catalytic TKP chemistry.
Interests and expertise (Subject groups)