The synthesis of hydroxy-iso-evoninic acid via a benzilic ester rearrangement
Author(s)
Warren, Sarah Ann
Type
Thesis
Abstract
Hydroxy-iso-evoninic acid is a pyridine diacid alkaloid present in nine natural products belonging to the Celastraceae plant family. The relative and absolute stereochemistry of the two stereocentres in this compound, which invariably occurs as a macrocyclic esterifying ligand between the C-3 and C-13 alcohols of β-dihydroagarofuran sesquiterpenes, were not assigned during isolation and no synthesis has yet been reported. The natural products containing hydroxy-iso-evoninic acid are of medicinal interest because of their high anti-HIV activity.
This thesis contains an overview of the pyridine alkaloids present in the Celastraceae plant family and background to the benzilic ester rearrangement (BER), a variant of the benzilic acid rearrangement (BAR) discovered by Liebig in 1838.
The majority of this thesis describes the first synthesis of the pyridine alkaloid hydroxy-iso-evoninic acid which utilises a BER as the key synthetic step. The development of a tunable diastereoselective BER is also reported, along with the initiation of the development of an asymmetric variant. The synthesis of a model of dihydro-β-agarofuran core euonyminol is also detailed to enable future assignment of the currently unknown stereochemistry of natural hydroxy-iso-evoninic acid.
This thesis contains an overview of the pyridine alkaloids present in the Celastraceae plant family and background to the benzilic ester rearrangement (BER), a variant of the benzilic acid rearrangement (BAR) discovered by Liebig in 1838.
The majority of this thesis describes the first synthesis of the pyridine alkaloid hydroxy-iso-evoninic acid which utilises a BER as the key synthetic step. The development of a tunable diastereoselective BER is also reported, along with the initiation of the development of an asymmetric variant. The synthesis of a model of dihydro-β-agarofuran core euonyminol is also detailed to enable future assignment of the currently unknown stereochemistry of natural hydroxy-iso-evoninic acid.
Date Issued
2011
Date Awarded
2012-02
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Spivey, Alan
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)