Evolved P450 mutants as general oxidation catalysts for target synthesis via early-/late-stage hydroxylation

This thesis describes the adoption of P450BM3 mutants as biocatalysts during target molecule synthesis in different stages and the efforts toward the synthesis of the azepane core type structure of natural product balanol and the enantiomer of natural product bulnesene. Chapter 1 provides an introduction to the application of P450BM3 mutants as oxidation catalysts for various structures including simple cyclic amines and sesquiterpenes. A review of the significance and various synthetic studies toward natural products balanol and bulnesene was provided. Chapter 2 describes a short demonstration of the feasibility of further functionalisation of P450BM3 hydroxylated cyclic amines by synthesising the azepane core of natural product balanol. Finally, Chapter 3 details a short enantiospecific route to ent-dihydrobulnesene and an investigation into the use of P450BM3 mutants for late-stage oxidation of sesquiterpenes, along with a comparison of P450BM3-mediated oxidation profiles of a pair of enantiomers