Degree Type

Dissertation

Date of Award

2014

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Nicola L. B. Pohl

Second Advisor

Jason S. Chen

Abstract

Carbohydrates are considered important biomolecules and are the most efficient sources of energy, which is the reason they are known as the "fuel of life." Apart from nutritional functions, they play significant roles in various cell-cell recognition and differentiation, inflammatory responses, pathogen invasion, etc. To understand their functions better, chemical syntheses of these crucial molecules have been attempted but scientists over the years have found this task to be challenging. Various worthwhile iterative methods/protocols have been developed and a range of glycosyl donors have been utilized to build oligosaccharides. Chapter 1 is a review on thioglycosides as important glycosyl donors in these processes. The chapter enlists common methods for their synthesis as well as accounts the available methods for their activation along with advantages/limitations.

In lieu of the existing limitations in thioglycoside activation, a simple and efficient methodology was developed for activating thiopropylglycosides utilizing a unique Bi(V) containing promoter. Chapter 2 discusses the successes and failures in synthetic trials towards the discovery of this promoter. A variety of glycosyl donors containing different protecting groups could be coupled to simple and complex glycosyl acceptors in high to excellent yields. The method does not require low temperatures, or additional additives/co-promoters and tolerates different functional groups including alkenes.

After the success of the developed method with alkene-containing compounds, it was applied to the acceptors containing alkynes. Chapter 3 describes how this strategy was utilized towards the synthesis of a particular alkynyl D-mannose analogue that was then coupled to a class of pentablock copolymers via Huisgen cycloaddition and quantified by various methods. The Mallapragada group has developed these copolymers as potential vaccine adjuvants candidates. Addition of carbohydrates like mannose to these adjuvants has proved helpful towards building protective immunity against viruses.

The bismuth-mediated thioglycoside activation protocol is one of the first demonstrations of Bi(V) in carbohydrate chemistry and to our knowledge, is also one of the first reports of using less than stoichiometric amounts of promoter in thioglycoside activation. These interesting features led to us to study this reaction in depth, with a vision to find possible ways to further improve the activation (make it catalytic), fasten reaction times, and also induce stereoselectivity in products. Chapter 4 constitutes a detailed mechanistic investigation of the activation with a variety of benchtop and analytical tools like 1D & 2D-NMR, GCMS, kinetics modeling etc. Role of various reactants on the rate of the reaction were studied as well as different by-product analyses were done. While studying the kinetics, an unprecedented isomerization was also discovered. This observation was utilized to improve reaction times and implement better diastereoselectivity in products. The hypothesis behind developing the activation protocol was based on the thiophilicity of bismuth and this was successfully probed as an in situ bismuth-sulfonium species could be detected by various NMR methods.

DOI

https://doi.org/10.31274/etd-180810-3687

Copyright Owner

Manibarsha Goswami

Language

en

File Format

application/pdf

File Size

194 pages

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