Document Type

Dissertation

Degree

Doctor of Philosophy

Major

Chemistry

Date of Defense

6-15-2011

Graduate Advisor

Alexei Demchenko, PhD

Committee

Professor Lana Stein

Michael R. Nichols, Ph. D.

Rudolph E. K. Winter, Ph. D.

Abstract

The important role that carbohydrates play in biology and medicine has been the major incentive for devising new methods for chemical and enzymatic glycosylation. The chemical approach to oligosaccharides involves multiple synthetic steps and the development of new strategies that allow for streamlining the synthesis of these complex biomolecules is a significant area of research. The aim of this doctoral dissertation is to develop new reagents and efficient methodologies for oligosaccharide synthesis. It was found that siver(I) tetrafluoroborate can be used as a powerful activator of various glycosyl donors for oligosaccharide synthesis. This study evolved into the development of a very effective orthogonal strategy which allowed for the synthesis of a variety of oligosaccharide sequences with moderate stereoselectivity. Further studies showed that the improvement of stereoselectivity of glycosylation can be achieved in two different modes. First, we found that electron withdrawing protecting groups on the glycosyl acceptor can help to obtain excellent alpha-stereoselectivity. Second, the stereoselectivity of glycosidation of thioglycosides in the presence of bromine depends greatly on the anomeric orientation of the leaving group. The mechanistic studies of this phenomenon were conducted using high field NMR and the developed methodology was applied to the synthesis of a range of therapeutically attractive carbohydrate-amino acid conjugates.

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