Studies on the total synthesis of aphidicolin
File(s)
Author(s)
Allen, Lewis Alexander Thomas
Type
Thesis
Abstract
In this thesis further developments on the thermal cascade reaction discovered in the Parsons group have been made. The substrate scope has been increased to include the ketone linked 1,6-diynes, which had failed to cyclise in previous studies. Furthermore, variations on the precursor molecule have led to the cyclisation of nitrogen and sulphur analogues to provide the respective annulated pyrrole and thiophene products. The synthesis of these compounds using the Parsons-Board-Waters cyclisation had not been explored during earlier studies within the group.
The increased scope of the Parsons-Board-Waters cyclisation was applied to the total synthesis of the natural product (+)-aphidicolin. The development of model systems are described, with the importance of the ketone functionality being highlighted by the unsuccessful cyclisation of dioxolane protected precursors. Furthermore, the enantioselective synthesis of a key intermediate containing the required 1,3-diol functionality present in the natural product is reported. This will provide a route to future research on the application of the Parsons-Board-Waters cyclisation to (+)-aphidicolin.
The increased scope of the Parsons-Board-Waters cyclisation was applied to the total synthesis of the natural product (+)-aphidicolin. The development of model systems are described, with the importance of the ketone functionality being highlighted by the unsuccessful cyclisation of dioxolane protected precursors. Furthermore, the enantioselective synthesis of a key intermediate containing the required 1,3-diol functionality present in the natural product is reported. This will provide a route to future research on the application of the Parsons-Board-Waters cyclisation to (+)-aphidicolin.
Version
Open Access
Date Issued
2015-10
Date Awarded
2016-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Parsons, Philip James
Sponsor
Parsons Scholarship
Bader Scholarship
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)