Good Book
Abstract
(1,3)-β-D-Glucans are naturally occurring polysaccharide polymers found in the cell walls of various fungi and bacteria. They are structurally composed of D-glucose polymers consisting of linear (1,3)-β-D-glucosidic linkages of varying length and also branched polymers with side chains attached as (1,6)-β-D-linkages. These side chains can be (1,3)-β or (1,6)-β glucoside chains of varying length. β-Glucans belong to a class of drugs called biological response modifiers (BRMs) due to their ability to activate the human innate immune system. Activation of the innate immune system occurs through recognition of β-glucans polymers expressed on cell surfaces of certain pathogens which are known as pathogen-associated molecular patterns (PAMPs). The PAMPs expressed on the cell surface of pathogens bind to complementary receptors called pattern recognition receptors (PRRs), such as Dectin-1, which initiates an immune response. Conclusions drawn from investigations aimed at the bioactivity of β-glucans is difficult due to problems associated with their isolation from nature. For this reason, access to synthetic β-glucans is in demand.
The research described in this thesis focused on the synthesis of (1,3)-β-D-oligosaccharides. We have successfully developed a convergent block-wise approach to the synthesis of high-molecular weight (1,3)-β-D-oligosaccharides. Key elements of this approach is the ability to selectively, and in good yield, deprotect the anomeric position and also control the stereoselectivity of the glucosidic couplings by neighboring group participation. Selective deprotection of the anomeric position was possible using the chloroacetate group. The chloroacetate group could be selectively deprotected in good yield and was found to be markedly superior to the benzoyl group recently employed by our group. Exclusive selectivity was achieved in the glucosylation of large substrates due to the stabilizing and participatory effect of the
(1,3)-β-D-Glucans are naturally occurring polysaccharide polymers found in the cell walls of various fungi and bacteria. They are structurally composed of D-glucose polymers consisting of linear (1,3)-β-D-glucosidic linkages of varying length and also branched polymers with side chains attached as (1,6)-β-D-linkages. These side chains can be (1,3)-β or (1,6)-β glucoside chains of varying length. β-Glucans belong to a class of drugs called biological response modifiers (BRMs) due to their ability to activate the human innate immune system. Activation of the innate immune system occurs through recognition of β-glucans polymers expressed on cell surfaces of certain pathogens which are known as pathogen-associated molecular patterns (PAMPs). The PAMPs expressed on the cell surface of pathogens bind to complementary receptors called pattern recognition receptors (PRRs), such as Dectin-1, which initiates an immune response. Conclusions drawn from investigations aimed at the bioactivity of β-glucans is difficult due to problems associated with their isolation from nature. For this reason, access to synthetic β-glucans is in demand.
The research described in this thesis focused on the synthesis of (1,3)-β-D-oligosaccharides. We have successfully developed a convergent block-wise approach to the synthesis of high-molecular weight (1,3)-β-D-oligosaccharides. Key elements of this approach is the ability to selectively, and in good yield, deprotect the anomeric position and also control the stereoselectivity of the glucosidic couplings by neighboring group participation. Selective deprotection of the anomeric position was possible using the chloroacetate group. The chloroacetate group could be selectively deprotected in good yield and was found to be markedly superior to the benzoyl group recently employed by our group. Exclusive selectivity was achieved in the glucosylation of large substrates due to the stabilizing and participatory effect of the