| beta-Mannosylation and alpha-sialylation has long been considered to be the most challenging glycosidic bond forming reactions to achieve in carbohydrate chemistry due to the inability of taking advantage of neighboring group participation chemistry and the need to override the anomeric effect. The bulk of this thesis focuses on methodology development to address such issues.;In beta-mannosylation area, a novel naphthylpropargyl protecting group has been developed based on the propargyl ether system. This group, when placed on the O3 position of 4,6-O-benzylidene protected sulfoxide donor, has been proven to be superb in terms of sterocontrol of glycosylation reactions. Its applicability in synthesis of complex sugar systems has been showcased in the convergent total synthesis of a beta-(1→3)-mannohexaose, in which the glycosylation reactions was all beta-selective. The only one exception was that of late stage combination of two trisaccharides fragments, when alpha/beta ratio was around 1:1.;In the alpha-sialylation field, an unusual 5-N,7- O-oxazinanone protected sialyl donor has been synthesized and its effect on the stereoselectivity of sialylation was subsequently investigated, leading to the conclusion that it was dentrimentral in terms of selectivity due to its deactivating tg conformation imposing on the sialic acid donor.;Given these negative results obtained with oxazinanone protecting strategy, alternative N-glycolyl 5-N,7-O-oxazolidinone protected admantanethio sialyl donor 171 was then studied. The donor 171 was found to behave in a much similar way as its earlier N-acetyl counterpart in terms of glycosylation selectivity, and could even allow a significant chemoselective glycosylation with reactivity-tuned thiogalactoside 189, which established the groud for a one pot synthesis protocol in sialylation area. The subsequent one pot synthesis of four Neu5Gc containing sequences was successfully achieved with excellent stereocontrol and reasonable yields. The extension of this efficient protocol to sialyl donor 51 was also illustrated with the one pot synthesis of GM3 ganglioside sugar skeleton. |
