Synthesis of Bacterial Oligosaccharides from N. meningitidis and Mechanistic Details of Stereoselective Glycosylations Using a Novel Bicyclic Donor
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
This thesis includes two parts. The first part, comprising Chapters 3, 4 and 5, describes the synthesis of bacterial oligosaccharides. In Chapters 3 and 4, the synthesis of branched and phosphorylated oligosaccharide structures corresponding to inner core epitopes of the lipopolysaccharide (LPS) of the Gram-negative bacteria N. meningitidis are discussed. A series of different spacer-equipped, phosphorylated and non-phosphorylated, glycosides has been synthesized as a part of a program involving development of a glycoconjugate-based vaccine against meningitis. Chapter 5 describes the synthesis of a tetrasaccharide corresponding to the repeating unit of the extracellular capsular polysaccharide (CPS) found in S. enteritidis. A short and efficient synthetic route to a trisaccharide acceptor corresponding to the common Gal-Man-Rha backbone found in several Salmonella O-antigen is presented. Further more, the synthesis of a novel tyveloside thioglycoside and the final glycosylation to assemble the complete target tetrasaccharide is reported.
The second part, Chapters 6 and 7, describes the development of a novel type of glycosyl donor, a 2N,3O-oxazolidinone protected bicyclic thioglycoside. This donor can be used in stereoselective glycosylations where, by tuning the reaction conditions, either complete α- or β-selectivity can be obtained from the same donor/acceptor system. A mechanistic explanation for this behaviour, involving initial formation of the β-anomer followed by a AgOTf-catalyzed in situ endocyclic anomerization to yield the more stable corresponding α-anomer, has been established. The suggested mechanism was supported by a series of NMR-experiments. Finally, in Chapter 7, the synthesis and use of a galacto-configured 2N,3O-oxazolidinone donor for the synthesis of a serine 2-acetamido 2-deoxy galactoside, a versatile building block for the synthesis of mucin O-glycan core structures, is discussed.
Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University , 2009. , 76 p.
oligosaccharide synthesis, heptose, thioglycoside, glycosylation, Neisseria meningitidis, 2, 3-oxazolidinone
Research subject Organic Chemistry
IdentifiersURN: urn:nbn:se:su:diva-29568ISBN: 978-91-7155-919-7OAI: oai:DiVA.org:su-29568DiVA: diva2:234190
2009-10-09, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Codée, Jeroen, Dr.
Oscarson, Stefan, Prof.
At the time of the doctoral defence, the following papers we unpublished and had a status as follows:
Paper 1: Manuscript. Paper 5: Manuscript2009-09-182009-09-062009-09-08Bibliographically approved
List of papers