Synthetic approaches to medicinally relevant euphorbia diterpenes

Thesis

This thesis is divided into six chapters. Chapter 1 provides an overview of the role of natural product synthesis in the 21st century, and provides a scientific and historical context for the research undertaken in this thesis, including prior work undertaken in the Jonathan W. Burton group towards the total synthesis of target compounds euphodendroidin D 1.17 and pepluanin A 1.18.

Chapter 2 provides a description our work on the synthesis of racemic cyclopentane 1.102 via a palladium-catalysed cyclisation, and the derivatisation thereof to racemic lactone 2.50. Chapter 3 covers our unsuccessful efforts to develop an enantioselective synthesis of 1.102, and our successful asymmetric synthesis of 2.50 via an alternative route. It also covers our extensive investigations into the allylic oxidation of 2.50.

Chapter 4 details our attempts to conduct a series of further redox manipulations, ultimately resulting in the scalable and high-yielding synthesis of 4.38, a densely functionalised intermediate, and the furthest point reached in our attempt to synthesise euphodendroidin D 1.17. Chapter 5 describes our asymmetric synthesis of 5.24, an advanced sulfone intermediate which was also necessary for our planned convergent synthesis of euphodendroidin D 1.17.

Finally, chapter 6 summarises our achievements and suggests a prospective improvement to the synthetic plan should the project be continued.

Authors: Sutro, JL

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: total synthesis; natural product synthesis
• Subjects: Synthesis