DEVELOPMENT AND SYNTHETIC APPLICATIONS OF BIOCATALYTIC METHODS: NATURAL AND NON-NATURAL ENZYMATIC REACTIONS

Abstract

Biocatalysis is a catalytic method that originates from nature and utilizes biological enzymesystems or specific enzymes. These enzymes are incredibly good at accelerating reaction rates with incomparable selectivity. Moreover, they can be precisely altered and tailored to particular reactions through directed evolution, which was awarded Nobel Prize in 2018. As a result, the biocatalytic process in organic chemistry has become even more powerful for synthesizing highvalue compounds. Consequently, it has been adopted into many pharmaceuticals' synthetic routes. Enzymes are excellent catalysts because they inherently bear excellent enantioselectivity and regioselectivity, high turnover numbers, and mild reaction conditions. However, enzymes are often recognized as particular catalysts for a narrow scope of substrates and reactivities, downgrading their general utilization in organic chemistry. In the first chapter, I summarized the general information about asymmetric catalysis, biocatalysis, and radical chemistry. In the second chapter, I outline my work utilizing commercially available enzymes and their natural functionality paired with a novel racemization mechanism to rapidly access libraries of enatio- and diastereo-enriched 1,2 amino alcohols. In the third chapter, I discussed my collaborative work with Dr. Yuxuan for developing evolved ‘ene’-reductases (EREDs) to control the highly reactive Nitrogen-Centered Radical (NCR) and catalyze an asymmetric radical intramolecular and intermolecular hydroamination reaction. In the last chapter, I complied three collaborative works with Dr. Haigen, Dr. Jose, and Claire on charge transfer complex-enabled photo-enzymatic enantioselective and regioselective C-C bond formation. Specially, Dr. Haigen and I utilized enzyme and charge transfer complex as a general platform for an enzymatic Csp3– Csp3 reductive cross electrophile coupling (XEC); Claire and I demonstrated a biocatalystcontrolled, charge transfer complex enabled method for the regioselective alkylation of electronrich and deficient heteroarenes; Dr. Jose and I took advantage of charge transfer complex and developed method to carry out radical cyclization using 620 nm red light.