The conceptually simple process of linking carbohydrate units by glycosylation has proven to be one of the most difficult synthetic processes to control from a stereochemical perspective. In particular it is the stereocontrolled synthesis of 1,2-cis glycosyl linkages (e.g. α-glucosides, β-mannosides) which poses the most difficult challenge. The research presented in this thesis describes new ways in which stereocontrol in glycosylation reactions can be achieved. New methods of neighbouring group participation have been explored, utilising novel protecting groups at the 2-postion of a series of glycosyl donors. In particular the use of glucosyl donors bearing a 2-O-(2-(2,4,6- trimethoxyphenyl)thio)ethyl protecting group at the 2-hydroxyl, have shown exceptional α-selectivity especially when a completely armed donor was used. Work within this thesis also describes the use of chiral Brønsted acid catalysts in stereoselective glycosylation reactions. However the yields and stereoselectivity obtained were not very encouraging.

Noncovalent and reversible covalent interactions have long been exploited in catalysis and supramolecular chemistry. Examples of such noncovalent interactions include hydrogen bonding, halogen bonding and CH-π and π-π interactions. Reversible covalent interactions that have been employed towards these ends comprise the formation of imines, acetals, ketals and boronate esters. This thesis describes the investigation of various noncovalent and reversible covalent interactions, and their possible applications in catalysis and novel reaction development. Chapter 1 describes the investigation of anion receptors composed of hydrogen- and halogen- bond donor groups. Binding studies of these molecules have indicated that they are capable of interacting with an anion simultaneously through hydrogen and halogen bonding. Receptor design was found to have a profound effect on the strength of the halogen bonding interaction. Receptors containing halogen-bond donors showed selectivity for halide anions over oxyanions. In Chapter 2, potential halogen bonding catalysts were synthesized and screened in a series of reactions. Incorporating halogen-bond donors into the catalysts appeared to have no beneficial effect in terms of reactivity. Explanations for these observations are discussed along with suggestions for designing future catalysts that could exploit halogen bonding interactions. Chapter 3 discusses attempts to use hydrogen-bond donor catalysts to effect catalyst-controlled stereoselective additions to 2-nitroglycals. While stereoselective additions were observed in some cases, they were not catalyst-controlled. The results from these experiments suggested that catalysts and reactions developed for simple nitroalkenes could not be easily adapted to 2-nitroglycal substrates. A review of interactions between boron containing compounds and saccharides is presented in Chapter 4. Their applications in drug delivery systems, cellular imaging and the sensing and separation of carbohydrates are discussed, in addition to their uses as protecting and activating groups in oligosaccharide synthesis. Finally in Chapter 5, the development of a regioselective boronic acid-mediated glycosylation reaction is described. This methodology was applied in the synthesis of two key intermediates used in the synthesis of a pentasaccharide derivative isolated from the plant Spergularia ramosa.

Noncovalent and reversible covalent interactions have long been exploited in catalysis and supramolecular chemistry. Examples of such noncovalent interactions include hydrogen bonding, halogen bonding and CH-π and π-π interactions. Reversible covalent interactions that have been employed towards these ends comprise the formation of imines, acetals, ketals and boronate esters. This thesis describes the investigation of various noncovalent and reversible covalent interactions, and their possible applications in catalysis and novel reaction development. Chapter 1 describes the investigation of anion receptors composed of hydrogen- and halogen- bond donor groups. Binding studies of these molecules have indicated that they are capable of interacting with an anion simultaneously through hydrogen and halogen bonding. Receptor design was found to have a profound effect on the strength of the halogen bonding interaction. Receptors containing halogen-bond donors showed selectivity for halide anions over oxyanions. In Chapter 2, potential halogen bonding catalysts were synthesized and screened in a series of reactions. Incorporating halogen-bond donors into the catalysts appeared to have no beneficial effect in terms of reactivity. Explanations for these observations are discussed along with suggestions for designing future catalysts that could exploit halogen bonding interactions. Chapter 3 discusses attempts to use hydrogen-bond donor catalysts to effect catalyst-controlled stereoselective additions to 2-nitroglycals. While stereoselective additions were observed in some cases, they were not catalyst-controlled. The results from these experiments suggested that catalysts and reactions developed for simple nitroalkenes could not be easily adapted to 2-nitroglycal substrates. A review of interactions between boron containing compounds and saccharides is presented in Chapter 4. Their applications in drug delivery systems, cellular imaging and the sensing and separation of carbohydrates are discussed, in addition to their uses as protecting and activating groups in oligosaccharide synthesis. Finally in Chapter 5, the development of a regioselective boronic acid-mediated glycosylation reaction is described. This methodology was applied in the synthesis of two key intermediates used in the synthesis of a pentasaccharide derivative isolated from the plant Spergularia ramosa.

The central theme of the research described in this thesis involves taking advantage of the reversible covalent interactions of organoboron species with diols, and exploiting them as catalyst-substrate interactions. Using this philosophy, novel catalytic transformations have been developed to form carbon-carbon and carbon-oxygen bonds. Chapter 1 describes a method that uses organoboron species to activate pyruvic acids in the direct aldol reaction with aldehydes. Formation of an anionic tetracoordinate boron adduct was the key step in the proposed mechanism. A wide range of aldehydes may be employed, delivering useful isotetronic acid products in high yields. The efficient synthesis of oligosaccharides requires methods for regioselective manipulation of hydroxyl groups in monosaccharides. Catalysis represents a potentially general solution to this problem, and recently, the development of catalyst-controlled methods towards this goal has intensified. Chapter 2 highlights the range of catalysts that may be exploited to alter the reactivity of hydroxyl groups in carbohydrates. Chapter 3 describes a novel diphenylborinic acid-catalyzed protocol, which enables the site-selective functionalization of carbohydrate derivatives and non-carbohydrate-derived 1,2- and 1,3-diols with a wide diversity of electrophiles. Mechanistic details of the organoboron-catalyzed processes are explored using competition experiments, kinetics and catalyst structure-activity relationships. These studies are consistent with reaction of a tetracoordinate borinate complex with the electrophilic species in the turnover-limiting step of the catalytic cycle. Chapter 4 further explores the utility of borinic acid activation in the first small-molecule-catalyzed glycosylation reaction of unprotected or minimally protected glycosyl acceptors. High levels of selectivity for the equatorial hydroxyl group of cis-1,2-diol motifs are demonstrated in reactions of several glycosyl acceptors using a variety of glycosyl halide donors. Chapter 5 describes a novel mode of catalysis using a boronic acid/Lewis base co-catalyst system. The proposed mode of activation involves the formation of a tetracoordinate adduct that displays enhanced nucleophilicity at the boron-bound alkoxide groups. This concept was applied to the regioselective silylation of carbohydrate derivatives as well as the desymmetrization of diols. Finally, Chapter 6 summarizes the work described in this thesis, discusses the challenges encountered in the development of the methodologies, and speculates on future directions that can be taken.

The central theme of the research described in this thesis involves taking advantage of the reversible covalent interactions of organoboron species with diols, and exploiting them as catalyst-substrate interactions. Using this philosophy, novel catalytic transformations have been developed to form carbon-carbon and carbon-oxygen bonds. Chapter 1 describes a method that uses organoboron species to activate pyruvic acids in the direct aldol reaction with aldehydes. Formation of an anionic tetracoordinate boron adduct was the key step in the proposed mechanism. A wide range of aldehydes may be employed, delivering useful isotetronic acid products in high yields. The efficient synthesis of oligosaccharides requires methods for regioselective manipulation of hydroxyl groups in monosaccharides. Catalysis represents a potentially general solution to this problem, and recently, the development of catalyst-controlled methods towards this goal has intensified. Chapter 2 highlights the range of catalysts that may be exploited to alter the reactivity of hydroxyl groups in carbohydrates. Chapter 3 describes a novel diphenylborinic acid-catalyzed protocol, which enables the site-selective functionalization of carbohydrate derivatives and non-carbohydrate-derived 1,2- and 1,3-diols with a wide diversity of electrophiles. Mechanistic details of the organoboron-catalyzed processes are explored using competition experiments, kinetics and catalyst structure-activity relationships. These studies are consistent with reaction of a tetracoordinate borinate complex with the electrophilic species in the turnover-limiting step of the catalytic cycle. Chapter 4 further explores the utility of borinic acid activation in the first small-molecule-catalyzed glycosylation reaction of unprotected or minimally protected glycosyl acceptors. High levels of selectivity for the equatorial hydroxyl group of cis-1,2-diol motifs are demonstrated in reactions of several glycosyl acceptors using a variety of glycosyl halide donors. Chapter 5 describes a novel mode of catalysis using a boronic acid/Lewis base co-catalyst system. The proposed mode of activation involves the formation of a tetracoordinate adduct that displays enhanced nucleophilicity at the boron-bound alkoxide groups. This concept was applied to the regioselective silylation of carbohydrate derivatives as well as the desymmetrization of diols. Finally, Chapter 6 summarizes the work described in this thesis, discusses the challenges encountered in the development of the methodologies, and speculates on future directions that can be taken.

Diastereoselective control of glycosylation still remains a difficult task. Therefore, new glycosylation methods using asymmetric catalysis were developed to control the diastereoselectivity. Two systems were developed and each focused on a separate type of glycosyl donor. In the first system, glycosyl halides were subjected to reaction conditions inspired by Hamilton et al., who effectively had controlled the substitution of a racemic chloroamine by an alcohol. Asymmetric control of glycosylation was achieved through this adapted catalytic system. Both enantiomers of the catalyst ((R) and (S) TRIP) generally displayed b-selectivity with tertiary butyl methyl ether (TBME) as the solvent allowing almost exclusive formation of the β-anomer. However, low and inconsistent yields were obtained. The second system proposed the use of the same phosphoric acid catalyst (TRIP) to catalyse the glycosylation of glycals. However, this was ineffective as the catalyst was not a strong enough Brønsted acid. These studies then led to the development of two new chiral catalysts which then promoted the glycosylation of glycals, along with the formation of an undesired side product. Attempts were made to reduce the formation of the side product but unfortunately this proved unsuccessful. The diastereoselective outcome displayed between the different catalysts in separate trials was negligible, but the principles developed in this study should lead to the further development of new chiral catalysts for the glycosylation of glycals.

No description available.

vi, 90 leaves : tables, graphs ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.1979) from the Dept. of Biochemistry, University of Adelaide

Thesis (Ph. D.)--Ohio State University, 2005. / Title from second page of PDF file. Document formatted into pages; contains xix, 347 p.; also includes graphics. Includes bibliographical references (p. 183-192). Available online via OhioLINK's ETD Center

Health benefits of the polysaccharide (1→3)-β-D-glucan, reported to induce immunobiological, hypocholesterolemic, and hypoglycemic, effects in humans and animals, have made the isolation, characterization, and assay of a viable glucan product critical. A new analytical method, based on internal standard proton NMR analysis, for the assay of solvent-wet samples containing (1→3)-β-D-glucan is presented. The method enables glucan identification, provides a solvent-free assay, and improves upon the previous multistep extraction and lyophilization procedure by reducing the 1-2 day analysis time to 1-2 h. NMR offers a rapid method for quantifying the glucan in commercial samples, such as nutraceuticals, as well as industrial samples enabling better evaluation of the efficacy, of these carbohydrates in health-related applications.