Deracemisation of Alcohols via Simultaneous Photocatalysis and Whole-cell Biocatalysis (thesis data)

This thesis outlines the research conducted on the application of concurrent stereoablative photobiocatalytic cascades and kinetic modelling on the deracemisation of secondary benzylic alcohols.
Chapter 1 introduces the motivation and fundamental concepts underlying this work, focusing on the benefits of photobiocatalysis, the mutual incompatibility within such dual catalytic systems, a literature review on the means for their co-adoption, and the modes of enantioconvergent catalysis this could enable.
Chapter 2 discusses the history and adaptation of a photocatalytic procedure for the oxidation of benzylic alcohols. Biocompatible media conditions were discovered to enable this facile transformation using sodium anthraquinone 2-sulfonate as a widely available, environmentally friendly, and water-soluble photocatalyst. Mechanistic studies supported the literature model for the photocatalytic cycle in addition to uncovering the significant degradation of the photocatalyst under our reaction conditions and the role of its two-electron reduced form as an electron sink under oxygen-limited conditions.
Chapter 3 details the generation and screening of a library of whole-cell biocatalysts expressing alcohol dehydrogenases for the asymmetric reduction of benzylic ketones, followed by reaction optimisation. Biocatalysts with Prelog- or anti-Prelog selectivity with coupled substrate cofactor regeneration were identified.
Chapter 4 discloses the construction of a concurrent linear photobiocatalytic cascade. Through extensive optimisation, a methodology for the deracemisation of secondary benzylic alcohols was developed, yielding significant improvements in efficiency and operational simplicity compared to previous reports. Trends and limitations in the substrate scope were discussed in terms of electronic properties and specific interactions with the biocatalyst.
Chapter 5 explores the application of kinetic modelling to extract additional information from time course datasets for deracemisation. Using the developed model, strategies for further reaction optimisation were preliminarily examined.
Chapter 6 summarises the outcome of the research presented herein and identifies promising directions for future work on concurrent photobiocatalytic linear deracemisation.