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|Title:||New Biocatalytic Methods for Selective Radical Reactions|
|Advisors:||Hyster, Todd K|
|Publisher:||Princeton, NJ : Princeton University|
|Abstract:||Biocatalysis is an emerging field that has become a mainstay in the pharmaceutical and fine chemical industries. In nature, enzymes have been evolved over millennia to cleanly and efficiently catalyze the syntheses of complex products under very mild conditions. These qualities of enzymes—efficiency, selectivity, and ease of operation—can be matched to the desired qualities of catalysts used in the laboratory synthesis of complex molecules. To have a more comprehensive application of biocatalysis in synthesis, new enzymatic reaction mechanisms must be developed with an aim for methods that are not only synthetically useful but also complementary to reactions catalyzed by transition metal- or small molecule catalysts. The focus of this thesis, therefore, lies in discovering new enzymatic reaction mechanisms. Chapter 2 describes a new activation mode for nicotinamide-dependent ketoreductases. Visible light irradiation initiates an intermolecular single electron transfer between reduced NADPH and α-bromo-lactones that form discrete charge-transfer complexes in the enzyme active site. The single electron transfer in the active site is followed by a stereoselective hydrogen atom transfer. Chapter 3 details an extension of light-induced single electron transfer in ketoreductases, now mediated by photoredox catalysis. The inclusion of the photocatalyst allows for an expansion in the substrate scope and utility of the previous work. Chapter 4 describes the application of newly discovered reactivity in flavin dependent ‘ene’-reductases to the highly selective radical cyclization of α-haloketone precursors. This work represents a novel C – C bond forming reaction for this enzyme class. Chapter 5 outlines initial investigations into a light-mediated, asymmetric remote radical functionalization catalyzed by ‘ene’-reductases controlled by the formation of a charge-transfer complex in the enzyme active site.|
|Alternate format:||The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: catalog.princeton.edu|
|Type of Material:||Academic dissertations (Ph.D.)|
|Appears in Collections:||Chemistry|
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