Synthesis of the ABC fragment of pectenotoxin-4

Thesis

This thesis details the application of two synthetic methodologies, developed by the Donohoe group, to the synthesis of the ABC fragment of pectenotoxin-4, a macrolide marine natural product that consists of 19 stereogenic centres, three tetrahydrofuran rings, one spiroketal and one bicyclic ketal embedded within a 26-membered macrocycle.

Pivotal to the developed synthetic route was the utilisation of an unprecedented cascade osmium catalysed oxidative cyclisation for the construction of two THF rings (the BC ring system). After successfully developing a model system for the synthesis of the AB anomeric 6,5 spiroketal, which involved the employment of a hydride shift initiated oxo carbenium ion formation followed by intramolecular spiroketalisation, the developed system was then applied to the fully elaborated synthesis of the ABC fragment.

The synthesis of the ABC fragment of pectenotoxin-4 was completed in 20 linear steps, with an overall yield of 3.3%.

Authors: Lipinski, RM

• Publication date: 2012
• DOI: 10.5287/ora-mjqb9077k
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: spiroketals; cyclization; catalysis; natural products; pectenotoxin
• Subjects: Heterocyclic chemistry; Organic chemistry; Natural products; Asymmetric catalysis; Organic synthesis; Synthetic organic chemistry