Eco-Friendly Synthetic Strategies for Organic Compounds: Insights into Biocatalysis and Flow Chemistry

Abstract

The ever-growing interest for sustainable chemical synthesis has led to the development of environmentally improved methodologies that reduce side effects on the environment while preserving synthetic efficiency. We report on the evolution of combining biocatalysis and flow chem from a complementary to a synergistic strategy for the synthesis of organic molecules. The studies are directed to develop and optimize biocatalytic methods with the use of enzymes and whole cells, establish integrated biocatalysis-flow chemistry approaches, and investigate efficient one-pot synthesis of primary amides catalyzed by scandium (III) triflatein under controlled microwave condition. Enzyme screening, process optimisation, flow chemistry integration and calculation of the molecular docking studies were used in an overall approach. It is shown that the reaction efficiency of this two-enzyme cascade system is greatly improved by ketoreductases (KREDs) reaching space-time yields of 8-47 g L⁻¹ h⁻¹ for the production of chiral alcohols, and exclusively high selectivity of lipase-catalyzed reactions with total turnover numbers >10⁷. This transaminase technology proved to be particularly productive with space-time yields of up to 25 g L⁻¹ h⁻¹ for chiral amine formation. The integration of flow chemistry led to an improvement in process control and scalability, in addition to enabling a 85% conversion of amide under optimised conditions. Combining biocatalysis with flow chemistry led to improved process control and scalability. The results provide a sound basis for sustainable organic synthesis based on the availability of environmentally friendly alternative to traditional chemical processes that are not only commercially viable but that are also all process efficient