The improved synthesis of two methyl glycosides, <I>viz</I> methyl 4-<I>O</I>-methyl-α-D-glucopyranoside and methyl 4-<I>O</I>-(α-D-glucopyranosyl)-α-D-glucopyranoside (methyl α-maltoside) from readily available starting materials is described for use as model compounds for oxidative studies of the industrially important polysaccharide amylose. Attempts to acetylate methyl-α-D-glucoside regioselectivity proved fruitless, whilst regioselective pivaloylation was more successful, albeit in yields of poor synthetic utility. In a variation to this approach, the glucoside, is synthesized <I>via</I> selective tri-<I>O</I>-benzoylation of methyl-α-D-glucoside with the regiospecificity of the reaction being a function of the relative strengths of intramolecular hydrogen bound rings, which are governed by the conditions under which the reaction is performed. In the second step, methylation of the free hydroxy group can only be achieved under pressure with silver oxide as catalyst. The target compound is obtained in the final step by conventional cleavage of the ester functions. Initial attempts to synthesise methyl-α-maltoside were convergent, being conducted with variants of the Koenigs-Knorr methodology and using reactions of previously prepared haloglucosides with variously protected 4-hydroxymethyl-α-D-glucosides. No combination of catalysts could be found to activate either of the substrates, or in an alternative strategy, mediate the reaction between a halomaltoside and an alkoxy nucleophile. The target maltoside is formed eventually <I>via</I> the selective anomeric deprotection of per-<I>O</I>-acetylated maltose, followed by stereospecific methylation in a manner similar to that described previously. It is found that in this penultimate step an intramolecular silver alkoxy - esteric salt inhibits mutarotation, thus allowing the predominant formation of the α-anomer. Further deacetylation gives rise to methyl-α-maltoside in 63% yield and in only three steps.

No description available.

No description available.

The novel <i>exo</i>-enzyme cleavable linker <i>N</i>-1-(4-(3-aminopropylcarbamoyl)-phenyl)ethylsulfanyl)-methyl)-1-phenylacetamide (1) was successfully synthesised and its potential for use in solid phase carbohydrate chemistry was investigated. Sugar substrates were synthesised in solution and attached to solid support <i>via exo</i>-linker 1, which is also cleavable under mildly acidic conditions. (Fig. 9963)

The aim of this project is to develop and test methodologies for conformational studies of free and bound GAGs. Gas phase conformations of heparin-derived oligosaccharides were studied by using Ion Mobility Mass Spectrometry (IMMS) and molecular modelling. Gas phase conformations were modelled using the AMBER force field. Their theoretical collision cross-sections were compared with the IMMS data and a good agreement was obtained. The gas phase conformations of heparin oligosaccharides were more compact than those observed in solution or crystal structures of heparin-protein complexes. This was attributed to the effects of sodium cations interacting with the negatively charged sulphate and carboxyl groups of oligosaccharides. Adiabatic maps of dihedral angles vs. potential energy of disaccharide fragments of the tetrasaccharides were calculated in the absence of the sodium cations. New NMR methods for the measurement of scalar and dipolar ¹H-¹H coupling constants and ¹³C-¹³C coupling constants in natural abundance ¹³C samples were developed. Performance of these methods was tested extensively. Solution conformation of the fully sulphated heparin-derived tetrasaccharide was studied by NMR spectroscopy. ¹H-¹H scalar coupling constants were used to characterize the dynamic equilibria of flexible monosaccharide rings. ¹H-¹H and ¹H-¹³C RDCs were used in the study of the conformation of the glycosidic linkages. RDC-refined structures were obtained from molecular dynamics with explicit water and sodium cations. Interactions of the heparin-derived fully sulphated tetrasaccharide with factor H modules, fH~19, 20 and fH~7, were studied using AUTODOCK. Conformation of a spin-labelled heparin-derived fully sulphated disaccharide was studied by NMR and molecular modelling.

No description available.

A route to <i>C</i>-glycosides and <i>C</i>-disaccharides with functionalised linkages has been investigated. This convergent strategy involves cycloaddition of selected alkenes and sugar derived nitrile oxide moieties. The resultant 2-isoxazolines can be modified and subsequently ring opened to afford compounds with carbonyl or amino containing linkages. The alkenes selected for study were two w-unsaturated monosaccharide derivatives: 5,6-dideoxy-1,2-<i>O</i>-isopropylidene-a-D-<i>xylo</i>-hex-5-enofuranose and methyl 5,6-dideoxy-2,3-<i>O</i>-isopropylidene-a-D-<i>lyxo</i>-hex-5-enofuranoside. Styrene, oct-1-ene and methylenecyclohexane were also studied as models. Four sugar based nitrile oxides were investigated in cycloadditions to these alkenes, based on D-glucose, D-galactose, D-mannose and L-fucose. Three complementary cycloaddition procedures were developed and evaluated: the dehydration of 2,6-anhydro-1-deoxy-1-nitroalditols, the hypochlorite-mediated oxidative dehydrogenation of pyranosyl oximes, and the dehydrochlorination of a pyranosyl hydroximoyl chloride. The oximes and hydroximoyl chloride compounds were synthesised from the corresponding pyranosylnitromethanes. Reactions involving the sugar oximes typically resulted in variable yields of the by-product furazan N-oxide (furoxan) in addition to the cycloadducts, depending on the dipolarophile reactivity. In contrast, uniformly high yields of cycloadducts (70-90%) were obtained from the nitromethyl compounds and hydroximoyl chloride with a range of dipolarophiles; little or no nitrile oxide dimerisation was observed in these reactions.

No description available.

Gum arabic was exposed to varying degrees of ionising gamma irradiation. The result confirms the lability of certain sugar and amino acid residues in the gum structure. A chemical deproteination was carried out on a gum arabic solution using butan-1-o1, and confirms previous results which indicate that the protein content of gum arabic cannot be totally isolated from the polysaccharide structure. Mild sequential Smith degradations were carried out on gum arabic, these degradations were less structurally destructive than previous periodate oxidations. Gum arabic was also fractionated by its ability to emulsify limonene oil and associate with its molecular surface. All the previous degradative studies give valuable structural information to elucidate the gum's heterogeneous branched nature. An analytical study was carried out on ten gum arabic samples of Sudanese and Nigerian origin, collected between 1950-1989. The gum's polysaccharide and amino acid composition were fully characterised and their emulsification stability determined. There are convincing indications that gum arabic has remained remarkably constant in chemical nature over the past 40 years. Seven gum exudates of the genus Albizia, four Acacia gum exudates and six Combretum gum exudates, all of which are not permitted as food additives, were analysed for their polysaccharide and amino acid composition. Food manufacturers require analytical data to characterise non-permitted gums to prevent their use as adulterants to substitute for gum arabic.

This work describes the development of a protecting group for sulfate monoesters in carbohydrates. After initial trial studies, the trifluoroethyl ester was selected as a suitable protecting group. The ester was formed from the sulfate by treatment with trifluoro diazoethane. This protection method is shown to be compatible with other common protecting groups used in carbohydrate chemistry. The protecting group is proven to be stable to the manipulations of many other protecting groups. The utility of monosaccharides incorporating protected sulfate esters in synthesis has been examined. It has been proven that they are useful and versatile building blocks in the synthesis of more complex structures. Selective cleavage of the trifluoroethyl ester was achieved with potassium <I>tert</I>-butoxide. The mechanism for this deprotection reaction has been studied and this investigation has led to the advancement of alternative deprotection methods.