Abstract
The overall objective of the research described in this thesis was to explore the field of glycosidic bond formation and degradation.
In more detail, the objective was to do further research in the field of highly reactive glycosyl donors. New ways of making highly reactive donors were explored and their properties in glycosylations were carefully examined. The physical chemistry aspects of conformationally changed donors were investigated with emphasis on the anomeric effect. Finally, neighboring group effects in glycosylations and hydrolysis of glycosides were investigated. The goal of this research was to develop new synthetic methods to evolve the field of synthetic carbohydrate chemistry. In addition, easy methods for obtaining complex oligosaccharides are needed to accommodate biochemical research and drug development. Furthermore, the aim was to shed light on the complex mechanisms of glycosylation and hy rolysis of glycosides. This mechanistic insight can then be used to develop new synthetic methods and obtain a better understanding of already existing methods.
In Chapter 1 general aspects of synthetic carbohydrate chemistry is described with an emphasis on elements that affects reactivity and selectivity of donors in glycosylations.
The remaining chapters describe the research performed during the last three years of PhD studies.
The work described in Chapter 2-5 is already published elsewhere; for that reason, the associated experimental procedures have been omitted, but they can be obtained from the published articles (See List of Publications). The research described in Chapter 2,4,5 and 6 was completed at the Department of Chemistry, University of Copenhagen under the supervision of Professor Mikael Bols. The work described in Chapter 3 was mainly conducted at Department of Chemistry and Biochemistry, University of Missouri-St. Louis, USA under supervision of Professor Alexei Demchenko.
In Chapter 2 the s nthesis of 2-O substituted methyl glycosides is described together with the rates obtained from their hydrolysis. The rates clearly show a correlation between the anomeric configuration and the type of functional group installed on the 2-OH.
In Chapter 3 the concepts of conformationally and anchimerically arming were combined in order to achieve the synthesis of a novel donor. The new donor’s capabilities in glycosylations are described.
In Chapter 4 a new method for making highly reactive glycosyl donors by 3,6-tethering is presented. The reactivity and selectivity of the new donors in glycosylation reactions are discussed.
In Chapter 5 the anomeric effect in flipped rhamnosyl donors was investigated. The anomeric effect was used as a tool in the search for β-selectivity in rhamnosylations.
In Chapter 6 β-selective mannosylations were investigated with the use of a 4,6-silylene tethering. The reason and the mechanism for the β-selectivity are discussed.
In more detail, the objective was to do further research in the field of highly reactive glycosyl donors. New ways of making highly reactive donors were explored and their properties in glycosylations were carefully examined. The physical chemistry aspects of conformationally changed donors were investigated with emphasis on the anomeric effect. Finally, neighboring group effects in glycosylations and hydrolysis of glycosides were investigated. The goal of this research was to develop new synthetic methods to evolve the field of synthetic carbohydrate chemistry. In addition, easy methods for obtaining complex oligosaccharides are needed to accommodate biochemical research and drug development. Furthermore, the aim was to shed light on the complex mechanisms of glycosylation and hy rolysis of glycosides. This mechanistic insight can then be used to develop new synthetic methods and obtain a better understanding of already existing methods.
In Chapter 1 general aspects of synthetic carbohydrate chemistry is described with an emphasis on elements that affects reactivity and selectivity of donors in glycosylations.
The remaining chapters describe the research performed during the last three years of PhD studies.
The work described in Chapter 2-5 is already published elsewhere; for that reason, the associated experimental procedures have been omitted, but they can be obtained from the published articles (See List of Publications). The research described in Chapter 2,4,5 and 6 was completed at the Department of Chemistry, University of Copenhagen under the supervision of Professor Mikael Bols. The work described in Chapter 3 was mainly conducted at Department of Chemistry and Biochemistry, University of Missouri-St. Louis, USA under supervision of Professor Alexei Demchenko.
In Chapter 2 the s nthesis of 2-O substituted methyl glycosides is described together with the rates obtained from their hydrolysis. The rates clearly show a correlation between the anomeric configuration and the type of functional group installed on the 2-OH.
In Chapter 3 the concepts of conformationally and anchimerically arming were combined in order to achieve the synthesis of a novel donor. The new donor’s capabilities in glycosylations are described.
In Chapter 4 a new method for making highly reactive glycosyl donors by 3,6-tethering is presented. The reactivity and selectivity of the new donors in glycosylation reactions are discussed.
In Chapter 5 the anomeric effect in flipped rhamnosyl donors was investigated. The anomeric effect was used as a tool in the search for β-selectivity in rhamnosylations.
In Chapter 6 β-selective mannosylations were investigated with the use of a 4,6-silylene tethering. The reason and the mechanism for the β-selectivity are discussed.
| Original language | English |
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| Publisher | Department of Chemistry, Faculty of Science, University of Copenhagen |
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| Number of pages | 110 |
| Publication status | Published - 2013 |