Doctor of Philosophy
Department of Chemistry
O'Meara, Gareth William, Asymmetric synthesis of glycosidase inhibitors, Doctor of Philosophy thesis, Department of Chemistry, University of Wollongong, 1999. http://ro.uow.edu.au/theses/1114
This thesis presents the results of studies aimed at the development of general strategies for the synthesis of azasugars, which act as glycosidase inhibitors. In the first Chapter a review is made of the role of carbohydrates and glycosidases in biological systems. The strategies developed for the synthesis of azasugars are discussed, as well as the aims of this project and the literature relevant to the synthetic aspects of this project.
The successful synthesis of γ-amino-α,β-unsaturated ketones from allylic sulfoximines utilising a palladium(O) catalysed rearrangement is presented in Chapter 2. The regioselectivities and diastereoselectivities of these transformations are also discussed.
In Chapter 3, the palladium(O) catalysed amination of allylic sulfoximines utilising external nucleophiles is described. The regioselectivities of these reactions with various allylic sulfoximines is reported, as are the results of competition reactions between the external nucleophile and the sulfinamide anion. The results of attempts to induce asymmetry into the reaction via the use of enantiomerically pure sulfoximines, chiral ligands and chiral external nucleophiles are also discussed.
The attempted synthesis of azasugars from allylic sulfoximines is presented in Chapter 4. Results from investigations into the use of both the intramolecular rearrangement examined in Chapter 2 and the allylic amination reaction described in Chapter 3 towards the synthesis of azasugars are detailed.
In Chapter 5, the attempted synthesis of azasugars from a carbohydrate source is reported. The key steps in the synthetic path are elongation via Grignard addition, palladium(O) catalysed allylic amination, oxidation of a double bond and cyclisation.
A brief summary of the work carried out in this thesis is provided in Chapter 6, as well as current and future work in this area.