Manufacture of Active Pharmaceutical Ingredients using Transition Metal Catalysts for Selective Functionalization of C-H Bonds

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The manufacture of Active Pharmaceutical Ingredients (APIs), the medicinally-active compounds in pharmaceuticals, is one of the key areas that can affect the cost and availability of new medicines. Through a collaboration between the University of Victoria and GlaxoSmithKline, we propose to develop new, more efficient methods to synthesize and manufacture APIs. We aim to turn ubiquitous carbon-hydrogen bonds in precursor molecules into more complex molecular structures by creating a new class of chemical catalyst. These catalysts will be designed specifically to activate and break the required carbon-hydrogen bond, and then deliver the activated molecule to a second catalyst for elaboration. This dual catalyst approach will enable independent optimization of both halves of the synthesis: breaking the carbon-hydrogen bond and forming a new carbon-carbon bond.To realize this goal, we will use high-throughput experimentation to rapidly evaluate catalyst candidates and map the chemical reactivity space in a multivariate manner. Not only will this accelerate discovery of active catalysts, but also provide a path toward larger-scale implementation through chemical process understanding. By targeting several in-development APIs at GlaxoSmithKline, rather than simple model systems, we will also ensure that our new catalysts are suitable for complex molecule synthesis.Ultimately, this research aims to streamline manufacturing processes for new medicines, reduce the amount of chemical waste generated during this manufacture, and drive down the cost of new medicines under development.