A novel approach to the synthesis of the FG fragment of pectenotoxin-4

Thesis

The cobalt-catalysed oxidative cyclisation of 5-hydroxy alkenes has been demonstrated to be a powerful synthetic tool for the formation of trans-THFs with excellent diastereoselectivity. This thesis describes the utilisation of this methodology in the synthesis of the FG fragment of pectenotoxin-4, allowing the scope of the reaction to be further explored.

Introduction: This section introduces the pectenotoxins, a family of structurally complex closed-chain polyether macrolides with promising biological activities. The isolation, structural elucidation, and biological properties of the pectenotoxins are reviewed, along with a summary of previous syntheses towards the FG fragment of pectenotoxin-4. In addition, the cobalt-catalysed oxidative cyclisation of 5-hydroxy alkenes and its application in synthesis is discussed.

Results and Discussion: An outline of the synthetic strategy employed in this project and details of the novel retrosynthesis of the C31-C40 fragment of pectenotoxin-4 is described. The synthetic studies carried out towards the synthesis of the FG fragment of pectenotoxin-4 are discussed in detail, with the exploitation of a cobalt-catalysed oxidative cyclisation as the key step to form the trans-THF F-ring. Overall, the FG fragment, which contains six stereogenic centres, was achieved in 18 total synthetic steps (13 longest linear sequence).

Authors: Luscombe, KN

• Publication date: 2012
• DOI: 10.5287/ora-0onx6qn87
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: pectenotoxin; cobalt; synthesis; Oxidative cyclisation; FG fragment; trans-Tetrahyrofuran; trans-THF
• Subjects: Organic synthesis; Organic chemistry