Document Type

Dissertation

Degree

Doctor of Philosophy

Major

Chemistry

Date of Defense

11-16-2018

Graduate Advisor

Alexei V. Demchenko

Committee

Eike B. Bauer

Janet Braddock-Wilking

Keith J. Stine

Abstract

Carbohydrates are the most abundant molecules among the four essential classes of biomolecules that also include nucleic acids, lipids and proteins. Unlike proteins and nucleic acids, which follow template-driven synthetic pathways, there is no general route to the synthesis of carbohydrates. The stereoselectivity of the formation of O-glycosidic linkages and the regioselectivity of protection and deprotection of specific hydroxyl groups over others represent two of the major challenges in carbohydrate chemistry. This thesis is dedicated to the development of novel strategies for efficient synthesis of carbohydrate building blocks and stereocontrolled glycosylations for step-economy oligosaccharide synthesis. Novel glycosyl donors with difluoro-3H-indol-2-yl (OFox) leaving group made from 3,3-difluoroxindole aglycone (HOFox) were investigated to achieve highly efficient glycosylation reactions. Moreover, the 2-O-benzyl-3,4,6-tri-O-acyl protecting group pattern helped to achieve high and even exclusive α-stereoselectivity. Based on the high reactivity of OFox imidates, regenerative glycosylation method was applied to glycosylations of bromide donors by using catalytic amount of HOFox to form OFox in situ. The synthesis of an important building block 1,3,4,6-tetra-O-acetyl-α-D-glucopyranose (2-OH glucose) was revisited and improved by better understanding of the reaction mechanism. Glycosyl nitrates were discovered to be the intermediates of this reaction. Glycosyl nitrates were also investigated as new glycosyl donors for O-glycosylation. Lanthanide triflates showed good affinity to activate the nitrate leaving group. The reaction conditions were further optimized and applied to the direct synthesis of oligosaccharides of 2-aminosugars, which previously required multiple synthetic steps.

Available for download on Friday, December 06, 2019

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