Chemical Synthesis of Complex Oligosaccharides from Bacterial Origin

Balasaria, Sakshi (2023) Chemical Synthesis of Complex Oligosaccharides from Bacterial Origin. PhD thesis, Indian Institute of Sciences Education and Research Kolkata.

Text (PhD thesis of Sakshi Balasaria (16IP005)) 17IP005.pdf - Submitted Version Restricted to Repository staff only Download (39MB)

Abstract

Carbohydrates are the most abundant molecules on Earth, after water. Their importance in our lives is so widespread that it is safe to say that every second several carbohydrates are working to keep us alive! Yet, they had been the least studied biomolecules for the longest time. The understanding of their vast functions and accepting them as the essential elements of life has begun just a few 100 years back. However these years have seen a rapid growth in the research and development related to these compounds. Starting from them being known as just energy transport and storage molecules to being recognized as potential vaccine candidates, the study of carbohydrates has come a long way. Carbohydrates are now used in several different fields like biotechnology, medicine, material science etc. This has been particularly possible with the advancement in synthetic methods of the saccharides. The thesis emphasizes the importance of oligosaccharides in different fields and their synthetic strategies. Their extraction from natural sources is cumbersome, hence synthesis is necessary. This is followed by the total synthesis of oligosaccharides which are obtained from bacterial cell walls and are antigenic in nature, thus serving as potential candidates for antibacterial vaccine designing. Chapter 1 gives a brief history of development of carbohydrates to the stage they are at today, followed by the importance of carbohydrates in our lives and their applications in modern day therapeutics. Chapter 2 describes the chemistry of carbohydrate synthesis – in particular related to a particular class of biologically important sugars i.e. amino sugars. A mini review on the synthesis of these sugars and the glycosylation strategies used for synthesis of oligosaccharides containing them, has been described. Also, some ways in which the synthetic oligosaccharides have been applied or can be applied as important biochemical tools has been illustrated. Chapter 3 deals with the Chemical synthesis of the pentasaccharide repeating unit of the O- antigen from Escherichia coli strain SDLZB008 in the form of its 2-aminoethyl glycoside. The aminoethyl linker could be used to attach the oligosaccharide repeating unit to a carrier protein for glycoconjugate vaccine designing. Chapter 4 deals with Total synthesis of the Tetrasaccharide repeating unit associated with the O-Antigen of Pseudomonas veronii SHC-8-1 containing rare 2-acetamido-2,4,6-trideoxy-4-(3,5- dihydroxyhexanoylamino)-D-glucose unit. The synthetic tools have been intelligently used for the synthesis of the challenging rare BacNAc moiety and its incorporation in a disaccharide. Also, amide synthesis with the 2-Hydroxybutyric acid has been illustrated. The particular strain has a potential application in the biotechnological field and, hence, the synthesis of the active oligosaccharide could be a step forward in this endeavour. Chapter 5 is about the Chemical synthesis of the pentasaccharide repeating unit of the O- polysaccharide from Escherichia coli O57. The consecutive 1,2-cis linkages in the repeating unit have been a challenge, however a large part of the target has been achieved using appropriate protecting group manipulations and stereoselective glycosylation strategies.

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