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Title: Evolved P450 mutants as general oxidation catalysts
Author: O'Hanlon, Jack
ISNI:       0000 0004 6494 0325
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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The thesis describes the use of a library of mutant P450BM3 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. Chapter 1 explores the P450BM3-catalysed oxidative cyclisation of α-amino (thio)acetamides for the synthesis of bicyclic imidazolidin-4-(thi)ones with P450BM3 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. Chapter 2 discusses the P450BM3-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. 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 P450BM3 variants for late-stage oxidation of intermediates to enable synthesis of the natural products themselves. Finally, the P450BM3-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.
Supervisor: Wong, Luet ; Robertson, Jeremy Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available