Organic photoredox catalysts as sustainable and cost-effective replacement for precious metal complexes in light-driven drug synthesis

PROJECT SUMMARYLight driven chemistryor photoredox catalysishas made significant advances in the last decade for practical organic or drug synthesisFor examplelight induced reactions have enabled generation of radical intermediate Rfor direct functionalization of biologically relevant heterocycles and cross coupling reactions for important covalent bond formationsThereforephotoredox catalysis offers tremendous potentials to access novel drug architectures not possible with conventional heat driven processesreduce drug synthesis stepsand improve process safetyall of which drastically reduce pharmaceutical manufacturing costsThese benefits have compelled drug companies to invest heavily in incorporating light driven chemistry to their next generation of pharmaceutical manufacturingFrom the public health s perspectivelight driven chemistry has the potential to substantially lower the cost to access therapeutics to improve overall human healthDihydrophenazine and phenoxazine organic photoredox catalystPCproductsa spin off innovation from the Miyake labare key to enable this photoredox revolution in the pharmaceutical industryDesigned to possess advanced photophysical propertieshighly reducingcharge transfer excited stateand redox reversibilitythese organic PCs dominate any PCsprecious metals or other organic PCsin the oxidative quenching applicationswhere an excited state reductant is requiredSpecificallydihydrophenazine and phenoxazine PCs has been demonstrated as cost effective replacement for precious metal iridium or ruthenium PCs in numerous radical induced and cross coupling reactionsIn some casesthese organic PCs were shown superior than iridium or ruthenium PCsfor examplethey were employed in lower catalyst loading and were used to discover novel chemistryIn this SBIR proposala number of technical hurdles associated with organic PCs commercialization will be resolved to de risk and ensure long term competitiveness of the companyIn Aimoptimization of synthetic routes was proposed for dihydrophenazine and phenoxazine synthesis to reduce production costIn Aimusing the optimized synthetic routesthe organic PCs production will be scaled up fromgweek tokgweekIn Aimto validate the performance of the organic PCs in an industrially relevant environmentthe organic PCs will be applied in kg scale drug intermediate synthesis using a photoflow reactorThe completion of this project will advance the organic PC products from Technology Readiness LevelTRLtoPROJECT NARRATIVELight driven chemistryor photoredox catalysishas made significant advances in the last ten years for practical organic or drug synthesisIt offers promises to access novel drug architecturesreduce manufacturing stepsand improve process safetyall of which drastically reduce drug manufacturing costsOrganic photoredox catalystsdeveloped in this SBIR Phase I proposalprovide cost effective and sustainable solutions to enable light driven chemistry in pharmaceutical manufacturing and therefore will substantially lower the cost to access therapeutics to improve overall human health