Total Synthesis of Conjugation-Ready Oligosaccharides from Bacterial Origin

Maiti, Sanajit (2026) Total Synthesis of Conjugation-Ready Oligosaccharides from Bacterial Origin. PhD thesis, Indian Institute of Sciences Education and Research Kolkata.

Text (PhD thesis of Sanajit Maiti (21RS102)) 21RS102.pdf - Submitted Version Restricted to Repository staff only Download (47MB)

Abstract

Bacterial O-antigens are relevant for their roles in bacterial adhesion to the host tissue. Owing to their antigenic character, they are often attractive targets for the development of carbohydrate-based vaccines against deadly microorganisms. Considering the complexity of isolation and purification of such saccharides from natural sources, chemical synthesis of the O-antigen repeats becomes the rational pathway for pure oligosaccharides in large quantity. The present thesis reports the total synthesis of such biologically active oligosaccharides from bacterial origin with suitable linker attached to the reducing end enabling them for further conjugation. The target oligosaccharides are challenging due the presence of rare sugars and difficult stereochemical requirements. Total chemical synthesis of three such oligosaccharides have been accomplished through rational protecting group manipulations and stereoselective glycosylations. Chapter 1 gives a general introduction to carbohydrates through its classifications and importance to various biological processes. The chapter also describes a few important carbohydrate containing drugs and antibiotics. Chapter 2 reviews the current challenges and development of the novel synthetic strategies for the construction of 1,2-cis glycosides. Considering the abundance and importance of the 1,2-cis linkages in biologically relevant oligosaccharides, the chapter provides important information on this area. Chapter 3 demonstrates the chemical synthesis of the trisaccharide repeating unit of the Oantigenic polysaccharide, isolated from Vibrio Cholerae O14, consists of one β-D-mannosamine unit, one α-L-rhamnose unit and a β-D-glucosamine unit. Further, an (S)-3-hydroxybutaryl group is attached to the amine part of the glucosamine moiety. Chapter 4 reports the total synthesis of the trisaccharide repeating unit of the OPS from A. brasilense Jm6B2 in the form of its 2-aminoethyl glycoside. As the target oligosaccharide contains Dacofriose, a practical and convenient route for the gram-scale synthesis of D-acofriose from commercially available D-mannose has been developed. Chapter 5 describes the total synthesis of the repeating unit related to the O-specific polysaccharide from Serratia sp. 10.1WK and 1XS having a trisaccharide repeating unit containing a β-D-mannose, a α-D-rhamnose, and a β-D-rhamnose. Chemical strategy for the introduction of Drhamnose units in both 1,2-trans and 1,2-cis fashion is particularly interesting as other important bacterial strains also have D-rhamnose units in their O-antigen repeats.

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