| Summary: | <p>The thesis describes the use of a library of mutant P450<sub>BM3</sub> variants for the biocatalytic oxidation of a range of structurally diverse substrates and the efforts toward the total synthesis of trigoxyphin K and L, employing biocatalytic C-H oxidation as a key step. <p>Chapter 1 explores the P450<sub>BM3</sub>-catalysed oxidative cyclisation of α-amino (thio)acetamides for the synthesis of bicyclic imidazolidin-4-(thi)ones with P450<sub>BM3</sub> variantcontrolled regio- and diastereoselectivity attainable in some cases. A method was developed for the Lewis acid-mediated ring-opening functionalisation of these compounds employing a variety of nucleophiles. <p>Chapter 2 discusses the P450<sub>BM3</sub>-catalysed para-hydroxylation of three sulfonanilidederived herbicides and the expansion of this transformation to a number of substituted anilides. Regioselectivity of hydroxylation was possible for certain substrates, with selectivity possible for para-hydroxylation or benzylic hydroxylation. <p>Chapter 3 details the successful approach to the core structures of the natural products trigoxyphin K and L and an investigation into the use of the library of mutant P450<sub>BM3</sub> variants for late-stage oxidation of intermediates to enable synthesis of the natural products themselves. <p>Finally, the P450<sub>BM3</sub>-mediated oxidation of a structurally diverse collection of small molecules and commercially available herbicides was examined with transformations including benzylic hydroxylation, acetal formation, S-oxidation, and nitro-group reduction.</p></p></p></p></p>
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