Organocascade reaction development: In cascade reactions, multiple synthetic steps are carried out in a single flask. Since a work-up and purification of each discreet synthetic transformation is not required, cascade reactions can greatly reduce the time, cost and waste (i.e., solvents, silica gel) associated with organic synthesis. An array of diverse molecular scaffolds can be accessed from the same simple starting materials.
Research
Organocatalysis
Organocatalysts are organic compounds that catalyze chemical reactions. The initial inspiration behind this field of research was to distill enzyme-like catalytic activity down to a single amino acid or amino acid-derived small molecule. Organocatalysis is complementary to traditional transition metal catalysis and enables green chemical methods to rapidly build molecular complexity, and is thus now firmly embedded in organic synthesis. The founders of this field of research were awarded the Nobel Prize in Chemistry in 2021. Within this field of research, our interests lie primarily in:
Dienamine catalysis: The inherent underlying challenges associated with catalysis via dienamine intermediates are catalyst control of regioselectivity, owing to multiple nucleophilic centers, and of stereoselectivity at the remote reactive center. We examine these issues through the lens of new reaction development, including organocascade reactions, sigmatropic rearrangements, and cooperative organo- and metal-catalyzed transformations.
Medicinal chemistry: We designed a fluorinated LpxC inhibitor based on a compound reported by Pfizer, and used our organocatalyzed fluorocascade reaction to synthesize it. LpxC inhibitors are potential antibiotic therapies for Gram-negative antibiotic resistant bacterial infections, notably because LpxC inhibition is a novel mode of action for antibiotics. Our compounds potently inhibited P. aeruginosa, one of the WHO’s priority pathogens.
Other research themes: sigmatropic rearrangements, (dynamic) kinetic resolutions, new catalyst design