Living vicariously - Merging biocatalysis and chemocatalysis for pyridine synthesis

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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.