| dct.abstract |
This thesis is about the glycosylation reactions of furanoses and their deriratives. Different types of glycosylation are: Oglycosylation, N-glycosyltion, C-glyccosylation and S-glycosylation. Important products are di- and oligosaccharides, nucleosides and deoxynucleosides, as well as C-alkyl furanosides and C-oligosaccharides. The focus of the thesis is the stereoselectivity of glycosylation, and how it can be affected by protecting groups, leaving groups, activation methods and acid/base ratio. In Oglycosylations, most studies are about arabinofuranosyl donor; while in N-glycosylation, ribose and deoxyribose are main issues. Both α- and β-anomer of O-, N- and C-glycosides have been synthesized by more than one method.
In most studies, neighboring group precipitation is used for the syntheses of sterically favored glycosides. For sterically unfavored glycosides, other method must be created. For instance, 2,3-anhydrosugars have been used as glycosyl donors in synthesis of Oglycosides, they avoid using of sterically demanding nonparticipating protecting group, but affect actively the stereochemistry in glycosylation step. This method can also give deoxyoligosaccharides. In syntehsis of ribonucleosides advantage is taken of 2'-O protecting group participation, whereas for synthesis of 2'-deoxynucleosides some examples of stereochemically directing 3'-O protecting groups have been introduced. Most often the glycosylation is an acid catalysed SN1 type process, with an oxocarbenium ion developing from the glycosyl donor. The detailed nature of the mechanism is widely discussed. Applications utilising direct displacement reactions are less common, but examples do exist. The third proposal is that the reaction goes through an endocyclic pathway, where the intermediate is acyclic.
In the experimental section, 6-cyano-5'-tert-butyldiphenylsilyl-3'-tert-butyldimethylsilyl-deoxyuridine was synthesized and further modification was tried. Because the difficulties in its synthesis, a model compound 6-cyano-1-tetrahydropyranyl-uracil was designed and synthesized quickly. The model compound was used in the tests with different reagents; the succeeded reaction was than tested on 6-CN-5'-TBDPS-3'TBDMS-deoxyuridine. Grignard reagent EtMgBr reacted with both compounds, but excess amount was needed. This may at least partly be due to the impurities in the starting material.
Also a base catalyzed two-phase hydrolysis was carried out on the model compound, the aim was to get carboxamide functionality; the reaction was examined in the mixture of water and tetrahydrofuran. The reaction was followed by HPLC chromatography. The chromatograms were analyzed in order to calculate the half-life of the starting material. |
en |
