Pre‐activation based glycosylations have become a very powerful tool in the assembly of oligosaccharides and the use of nucleophilic additives allows for the in situ generation of reactive... Show morePre‐activation based glycosylations have become a very powerful tool in the assembly of oligosaccharides and the use of nucleophilic additives allows for the in situ generation of reactive intermediates with tailored reactivity. We here use a glycosylation strategy that is based on the use of per‐benzylated imidate building blocks for the fully stereoselective construction of a spacer equipped Aspergillus fumigatus α‐1,3‐octaglucan. We have used the trimethylsilyl iodide (TMSI)‐triphenylphosphine oxide (Ph3P=O) for the stereoselective installation of an azidopropanol spacer and triflic acid (TfOH)‐dimethyl formamide (DMF) enabled glycosylations for the coupling reactions with the secondary glucosyl C‐3‐alcohols. An operationally simple in situ activation coupling procedure is introduced and used for the final glycosylation events towards the octasaccharide. Show less
The work in this thesis has been focused on two subjects. The first is the assembly of alginate oligosaccharides and the generation of building blocks for the enzymatic synthesis of alginate,... Show moreThe work in this thesis has been focused on two subjects. The first is the assembly of alginate oligosaccharides and the generation of building blocks for the enzymatic synthesis of alginate, and the second is the total synthesis of large fragments of the zwitterionic SP1 polysaccharide. With these fragments, details about alginate biosynthesis can be obtained through binding studies with biosynthesis enzymes, conjugate vaccines can be generated and binding studies with major histocompatibility complex II molecules can be studied. Show less
The thesis focuses on synthesis strategies in oligosaccharide campaigns, and the influence of protecting groups. New protecting group deprotection methods and protecting groups are developed.... Show moreThe thesis focuses on synthesis strategies in oligosaccharide campaigns, and the influence of protecting groups. New protecting group deprotection methods and protecting groups are developed. These novelties are applied in the synthesis of oligosaccharides which represent interesting biological targets. A solid phase approach is used to construct a library of oligorhamnans, employing a protecting group developed in this thesis. A fast deprotection method is employed to selectively remove fucntionalized benzyl ethers, which allows for the introduction of functional groups on a mannuronic acid molecule. Future synthesis campaigns are drafted combining the methods used in the previous chapters. Show less
Maier, M.; Reusch, D.; Bruggink, C.; Bulau, P.; Wuhrer, M.; Molhoj, M. 2016
In this thesis new strategies towards biologically active oligosaccharides are described. In addition a detailed mechanistic study is performed to investigate the stereodirecting capacity of... Show moreIn this thesis new strategies towards biologically active oligosaccharides are described. In addition a detailed mechanistic study is performed to investigate the stereodirecting capacity of glycosyl C-5 substituents in systems that were devoid of any other stereodirecting factors. The postulated mechanism described here can aid in the design of glycosylation strategies. Show less
Schistosomiasis, also known as bilharzia, is a disease that still occurs in many parts of Africa, the Middle East and Southern America, mainly Brasil and the Caribbean. Schistosomiasis is, after... Show moreSchistosomiasis, also known as bilharzia, is a disease that still occurs in many parts of Africa, the Middle East and Southern America, mainly Brasil and the Caribbean. Schistosomiasis is, after malaria, the second most common parasitic infection. Currently 200 million people are infected with the worms that cause the disease. Schistosoma mansoni is the most common schistosome species that infects humans. The schistosome produces many different sugar structures (glycans) that are not made by humans. Central to this thesis are sugar structures with a __double fucose__. Such fucosylated glycans are mainly produced by the eggs, which play a major role in the disease schistosomiasis. The human immune defence system responds to these parasite glycans in several ways. High antibody responses have been measured against sugar structures with a __double fucose__ moiety and different types of immune cells interact with these glycan structures. Despite these immunological responses the human host is not able to clear the parasitic infection. Glycans are thought to play a role in the mechanisms that S. mansoni has developed to survive in the hostile environment of the human blood. In this thesis the structures of several glycans containing the __double fucose__ moiety have been characterised using different mass spectrometric techniques. Show less
