Evolved P450 mutants for streamlining synthesis via late-stage C-H activation

Thesis

This thesis describes synthetic studies towards the carbon framework of the natural product viridiol and the application of mutant P450 enzymes to effect late-stage oxidations on these substrates.

The introduction provides a short summary of existing C-H activation and biocatalytic strategies in synthesis. An overview of P450 enzymes is also given and the background of viridiol and past synthetic studies are discussed.

Chapter 1 explores the construction of the ABE tricycle of viridiol, starting from the furan unit.

Chapter 2 introduces an alternative synthetic approach, focusing on the synthesis of the steroidal core from cyclohexenyl and 4-indanyl fragments. The challenges encountered in the preparation of single regioisomers of the indanyl system are also discussed.

Chapter 3 describes the development of an efficient route to 4-substituted indanes.

Chapter 4 continues the synthesis of the steroidal core from the 4-indanyl unit and details the completion of the viridiol carbon framework.

Chapter 5 investigates the late-stage oxidation of both tri and tetracyclic substrates with mutant P450 enzymes.

Authors: Atkinson, V

• DOI: 10.5287/ora-vjdnxekxx
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: C-H Activation; Cytochrome P450; Organic Synthesis; Enzymes; Steroidal Scaffold; Indanes; Natural Product Synthesis; Enzymatic Oxidation; Biocatalysis; Viridiol
• Subjects: Chemistry, Organic