Chemical Synthesis of Biologically Active Oligosaccharides

Adak, Anirban (2021) Chemical Synthesis of Biologically Active Oligosaccharides. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Anirban Adak (16RS009)) 16RS009.pdf - Submitted Version Restricted to Repository staff only Download (5MB)

Abstract

Carbohydrates are natural biopolymers responsible for various biological processes like energy storage, energy transport, structural motifs and most importantly as information carriers. They are the most abundant biomolecules on the Earth. However, their importance is neglected for long time. Only recently the carbohydrates are also regarded as one of the important biomolecules along with proteins and genes. The present thesis demonstrates the importance of chemical synthesis of the oligosaccharides. It may be argued that the biologically relevant oligosaccharides may be isolated from the natural sources. However, isolation of oligosaccharides in adequate quantity and acceptable purity is not an easy task if not impossible. Therefore, chemical synthesis of a particular oligosaccharide structure is the only option if one wants to elucidate the real biological implication of that particular structure. Chapter 1 introduces the reader to the world of carbohydrates through their genesis, classifications, importance in various biological processes and their use in modern day therapeutics. Chapter 2 describes the challenges of chemical synthesis and reviews the literature reports on chemical O-glycosylation methods that enable us to construct desired glycosidic linkages with proper regio- and stereoselectivity Chapter 3 illustrate the chemical synthesis of the 4-amino-4,6-dideoxy-D-glucose containing pentasaccharide repeating unit of the O-specific polysaccharide from Aeromonas hydrophila strain K691 in the form of its 2- aminoethyl glycoside. This chapter also shows the path for synthesis of rare sugar moiety 4- amino-4,6-dideoxy-D-glucose from known D-fucose derivative. Chapter 4 describes a concise synthetic strategy for the synthesis of the tetrasaccharide repeating unit of the O-antigen from Escherichia coli O131 containing N-acetyl neuraminic acid. It is always difficult to incorporate N-acetyl neuraminic acid in a chemical glycosylation as the thioglycoside is reluctant for effective activation. However, we have accomplished the glycosylation through activation of S-ethyl glycoside. Chapter 5 details the synthesis of hexasaccharide repeating unit of the exopolysaccharide of Lactobacillus mucosae VG1. In this particular synthesis the regioselective glycosylation of primary hydroxyl group in the presence of a free secondary hydroxy group is the key and this regioselectivity in turn helped us to minimize the protecting group manipulations. All of these oligosaccharides reported in the present thesis are synthesized in the form of their 2-aminoethyl or 3-aminopropyl glycosides. The free amine at the terminal will allow further glycoconjugate formation without hampering the anomeric stereochemistry.

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