Living vicariously - Merging biocatalysis and chemocatalysis for pyridine synthesis

This project will develop new syntheses of pyridines, one of the most important motifs in drug structures, using biocatalysis merged with chemocatalysis, using the idea of integrated catalysis - the concurrent use of chemo- and bio-catalytic transformations to enable novel synthetic pathways that were not previously possible. Tandem processes are a hallmark of atom-efficiency and can substantially reduce the environmental footprint of chemical processes - an axiom of sustainable synthesis for the future. The integrated approach will be driven by the complementarity of the two modes of catalysis - TM-catalysed processes such as C-H activation and photoredox chemistry offer a new approach to C-C bond formation using unactivated substrates, and biocatalysis brings tremendous power in terms of stereo-controlled functional group manipulation. Together, they offer a new way of building up molecular complexity whilst simplifying process complexity and cost.
The project will address the following major challenge: How can we create mutually compatible reaction conditions for both enzymes and organic synthesis systems, given the often vastly different requirements (notably of temperature and solvent)? A solution to this problem would have far-reaching significance to industrial/manufacturing chemistry, enabling synthetic routes to be dramatically streamlined and accelerated. If we can define pairs of bio/chemo catalysts that are proven to work in synergy, we can provide a modular approach to synthesis whereby valuable motifs (e.g. chiral secondary alcohols/amines, sulfoxides, all alkyl stereocentres etc.) are assembled with unprecedented speed and versatility.