Synthesis of the CDE & EFG ring systems of pectenotoxin-4

Thesis

This thesis explores new synthetic routes for the formation of CDE & EFG fragments of pectenotoxin-4.

Chapter 1: Introduction and Previous Work

This chapter reviews the discovery and biological activities of members of the pectenotoxin family. Two previous total syntheses are discussed, and previous work regarding the synthesis of ABC, E and FG fragments within the group is introduced.

Chapter 2: Synthesis of the E Ring Fragment of Pectenotoxin-4

The synthesis of the E ring fragment is discussed. Key reactions include Negishi coupling and osmium mediated oxidative cyclisation.

Chapter 3: First Generation Strategy for the Synthesis of the D ring

A simple model towards the D ring core was completed using alkyne-epoxide opening strategy. The application on a more sophisticated system was tested.

Chapter 4: Second Generation Strategy for the Synthesis of the D ring

Sonogashira coupling was successfully tested as key step to unite two coupling partners; and further functionalisation towards the D ring skeleton was studied.

Chapter 5: Third Generation Strategy for the Synthesis of the D ring

The new strategy including a Lewis acid assisted coupling and mercury mediated hydration of alkyne sequence was completed on a simple model. The application on a more sophisticated system was tested.

Chapter 6: Synthesis of EFG Fragment of Pectenotoxin-4

Key Julia−Kocienski olefination between E ring fragment and FG ring fragment was examined. The further functionalisation of the resulting coupling product towards EFG fragment was finished.

Chapter 7: Experimental

Full experimental procedures and characterisation of compounds are reported.

Authors: Liu, Y

• DOI: 10.5287/ora-nbzmdbq2o
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: total synthesis; pectenotoxin; organic chemistry; synthetic organic chemistry
• Subjects: Chemistry, Organic