Thesis--Cambridge. / Typescript (carbon) with ms. corrections. Includes bibliographical references.

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This thesis describes the synthesis of three novel seven carbon bicyclic mimics of α-L-fucose, and of two new pyrrolidine amino sugars. 2,7-Anhydro- l-deoxy-β-L-gulo-heptulopyranose and l,2,7-trideoxy-2,7-imino-β- L-gulo-heptulopyranose were both synthesised from L-gulono-l,4-lactone. The addition of one equivalent of methyllithium to the diacetonide of L-gulono-1,4- lactone gave a keto-sugar, l-deoxy-3,4;6,7-di-0-isopropylidene-β-L-gulo- heptulofuranose. The anomeric configuration of this compound was determined by equilibrium nOe measurements. Hydrolysis in aqueous trifluoroacetic acid caused simultaneous deprotection, isomerisation and dehydration to yield 2,7-anhydro-l-deoxy-β-L-guloheptulopyranose, a highly stable, rigid bicyclic system. The structure of the bicyclic system was confirmed by X-ray crystallographic studies on a crystalline derivative. The introduction of nitrogen at C-6 of L-gulono-l,4-lactone was achieved via the azide displacement of the known bromide, 6-bromo-6-deoxy-2,3-0- isopropylidene-L-gulono-l,4-lactone. Protection of the C-5 hydroxyl group as its silyl ether was followed by the addition of one equivalent of methyllithium to the carbonyl group to give a keto-sugar, 7-azido-6-(0-tert-butyldimethylsilyl-l,7- dideoxy-3,4-0-isopropylidene-β-L-gulo-heptulofuranose. Removal of the protecting groups followed by reduction of the azide functionality gave the bicyclic hemiaminal, l,2,7-trideoxy-2,7-imino-β-L-gulo-heptulopyranose, a stable but hygroscopic solid. A third bicyclic system, 2,7-anhydro-l,2,6-trideoxy-2,6-imino-β-L-gulo- heptulopyranose, was synthesised from diacetone-D-mannose via the known ketosugar, 6-azido-7-0-tert-butyldimethylsilyl-l,6-dideoxy-3,4-0-isopropylidene-β- L-gulo-heptulofuranose. Removal of the protecting groups from this keto-sugar, followed by reduction of the azide functionality, gave the target system. Analysis of the NMR spectra showed that this existed as an equilibrium mixture of the closed, bicyclic hemiaminal form and the monocyclic imine form, with the bicyclic form predominating in all solvents investigated. The sodium borohydride reduction of l-deoxy-3,4;6,7-di-0-isopropylidene-β-L-gulo-heptulofuranose gave a single product, the heptitol 7-deoxy-l,2;4,5-di-0-isopropylidene- L-glycero-D-gluco-heptitol. This was converted into two novel pyrrolidine amino sugars, l,2,5-trideoxy-2,5-imino-L-glycero-L-allo-heplitol and l,2,5-trideoxy-2,5-imino-L-allitol. The two free hydroxyl groups in the heptitol were converted into leaving groups and one was then displaced selectively with sodium azide. Reduction of the azide functionality gave an amine which cyclised onto the remaining leaving group to form the pyrrolidine framework. Complete deprotection of this product gave l,2,5-trideoxy-2,5-imino-L-glycero-L-allo- heptitol, the structure of which was confirmed by X-ray crystallographic studies on a crystalline derivative. Removal of the primary acetonide from the cyclisation product and subsequent periodate cleavage gave an aldehyde which was then reduced to an alcohol. Deprotection then gave the second pyrrolidine amino sugar l,2,5-trideoxy-2,5-imino-L-allitol. The effect of all five target compounds on eleven human liver glycosidase enzymes was investigated, and these results are also reported.

Graduation date: 1956

Thesis (PH. D.)--University of Nebraska, 1930. / Description based on print version record. Bibliography: p. 20.

D.Sc. (Chemistry) / Please refer to full text to view abstract

M.Sc. (Chemistry) / The aim of this study was to investigate the oxidation of aromatic compounds and benzylidene acetals with dimethyldioxinne. Dimethyldioxirane, either by Insitu preparation or in the isolated form, has shown remarkable reactivity. This oxidant is effective in oxygen transfer, readily prepared from commercial materials and reacts under mild conditions. Quinones are natural materials with biological activity and some are key intermediates in the synthesis of medicines. A well-known method for the preparation of quinones, is the oxidation of phenols and aromatic ethers. The oxidation of simple phenol and anisole derivatives by dimethyldioxirane yielded complex mixtures. More hindered aromatic compounds were investigated, since the oxidation of these compounds proceeded in a more controlled manner. In this study the phenols were found to be more reactive than the corresponding aromatic ethers. para-Quinones were formed preferentially, whereas ortho-quinones were observed in one or two cases. Products formed in these oxidations depend on the substitution pattern of the substrate. The oxidation of phenols and aromatic compounds formed complex mixtures and does not have many synthetic applications. Mechanisms are proposed for the formation of the different products. Benzylidene acetals are important protecting groups in the chemistry of carbohydrates. Cleavage of these benzylidene acetals gave either the free diol or benzyl ether or benzoyl ester, depending on the reagent used. The reaction of dimethyldioxirane with benzylidene acetals gave the benzoylesters. With dioxanes, e.g. 4,6-O-benzylidene sugar derivatives, there are no difference in stereoelectronic effects in the cleavage of C-4 and C-6. The major product has a 6-benzoate group, probably due to the greater stability of the primary benzoate. In dioxolanes both reactivity and regioselectivity of the reactions are influenced by stereoeleetronic effects. It has been found that the cleavage of dioxolanes took place preferably in a conformation where the oxygen is antiperiplanar towards the leaving group. It has been shown that dimethyldioxinme can be used with success in the deprotection of benzylidene acetals in the chemistry of carbohydrates.

The purpose of this work was the preparation of specifically blocked D-glucose derivatives with a free hydroxyl group on the anomeric carbon (C-1).

No description available.

No description available.