Chapter 1 comprises a general introduction to the field of chemical carbohydrate synthesis. The work since 1984 that has had a profound influence on the development of 1,2-diacetal mediated reactivity tuning is summarised. Chapter 2 examines the applicability of 1,2-diacetal mediated reactivity tuning to oligosaccharides assembly. In particular, the use of the butanediacetal protecting group (BDA) to tune the reactivity of glycosyl fluorides is disclosed. The application of this methodology enabled the first one-pot assembly of a linear pentasaccharide from monosaccharide building blocks. Chapter 3 focuses on synthetic advances towards the Glysosylphosphatidylinositol (GPI) anchor of yeast <I>Saccharomcyes cerevisiae</I> I and analogues of the conserved GPI core structure. The synthesis the full carbohydrate core structure of I was completed by application of this new methodology. In addition, the development of a flexible strategy towards I enabled the examination of parallel routes to GPI analogues.

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This thesis is divided into four chapters. The first contains an introduction to oligosaccharides, including an overview of their role in nature and a summary of the difficulties and complexities in saccharide synthesis in the context of protection strategies. Selective glycosylation reactions, by control of donor reactivity, and the development of the armed/disarmed concept for saccharide coupling are discussed. The second chapter concerns research into the scope of selective glycosylations using competition reactions to evaluate the effects of protecting groups on the reactivity of glycosyl donors. A variety of protecting groups are studied with both rhamnose and mannose monosaccharides. The influence of the sugar type and of different anomeric leaving groups is also discussed. The third chapter deals with the application of data from chapter 2 to the design of oligosaccharide syntheses. A trisaccharide synthesis is planned whereby the protecting group strategy is developed to tune the reactivity of the monosaccharide building blocks. This enabled a "one-pot" procedure to be implemented, demonstrating the suitability of this methodology to the efficient synthesis of oligosaccharides.

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The work within this thesis describes the optimisation of the synthesis of a series of [l,4]-morpholines, [l,4]-oxazepanes and disaccharide mimics prepared by reductive amination of carbohydrate-derived dialdehydes with primary amines. Also described are the investigations into synthesis of heptanoside motifs via nitroaldol reactions of carbohydrate-derived dialdehydes and Beckmann rearrangements of carbohydrate oximes. Chapter 1 provides an introduction to the involvement of carbohydrates within biological pathways, with particular interest in monosaccharide; importance and the methodologies used in the synthesis of heptanoside motifs. Chapter 2 provides an overview of oxidative cleavage, reductive amination and nitroaldol reactions with particular emphasis on the application of these reactions to carbohydrate substrates.

The first part of this thesis describes the synthesis, solution studies and biological evaluation of 2-keto-3-deoxy-ulosonic acids. A synthetic route was developed for 2-keto- 3-deoxy-gluconate (o-KDG) and 2-keto-3-deoxy-galactonate (D-KDGal) that provided the targets via concise four step routes from naturally occurring sugar substrates. These routes make use of Horner-Wadsworth-Emmons reactions between the anion of ethyl 2- ((terl-butyldimethylsi lyl)oxy)-2-(dimethoxy-phosphoryl) acetate 1 with enantiopure sugarderived aldehydes to afford silyl-enol et hers that cou d be globally deprotected to give the target 2-keto-3-deoxy-ulosonic acids in high purity (Scheme I). The effect of temperature on the isomeric composition of these C6-sugars was studied and they were then supplied as substrates for the directed evolution of a stereochemically promiscuous aldolase from Sulfolobus solfataricus, to develop mutant aldolases with high diastereoselectivity for the aldol reaction of D-glyceraldehyde 6 and pyruvate 7 to exclusively afford either D-KDG or D-KDGal. The synthetic methodology was then applied to the synthesis of enantiopure 2-keto-3- deoxy-D-xylonale (D-KDX) and 2-keto-3-deoxY-l-arabonate (l -KDA) and these C5-sugars were fully characterised by 1H and DC NMR spectroscopy for the first time and had their enantiopurity confirmed by optical rotatory dispersion analysis. The kinetic parameters for D-KDX and L-KDA using KOG aldolase were determined using a modified thiobarbituric aCid assay, with good catalytic efficiencies being found for each. enantiomer (0.45 and 0.53 s•1mM•1). This gives a more complete understanding of the metabolism of S. solfataricus confirming that the archaeon uses the same KDG aldolase for the catabolism of not only the diastereotopic C6-sugars D-KDG and D-KDGal but also for the ' enantiomeric CS-sugars D-KDX and L-KDA.

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