Document Type

Dissertation

Degree

Doctor of Philosophy

Major

Chemistry, Organic

Date of Defense

10-28-2022

Graduate Advisor

Prof. Alexei V. Demchenko

Committee

Prof. Eike B. Bauer

Prof. Janet Braddock-Wilking

Prof. Keith J. Stine

Abstract

This thesis is dedicated to the development of new methodologies for efficient synthesis of carbohydrate building blocks and their application to chemical glycosylation. S-Indolyl (SIn) anomeric moiety was investigated as a new leaving group. Understanding of the reaction pathways for the SIn moiety activation was achieved via the extended mechanistic study. The activation profile of indolylthio glycosides required large excess of activators. This drawback was partially addressed by the development of N-alkylated SInR derivatives. The activation process was studied by NMR and the increased understanding of the mechanism led to a discovery of different activation pathways taking place with SIn versus SInR derivatives. Also investigated was orthogonality of the SInR leaving groups versus other building blocks.

The synthesis of a common 3-OH glycosyl acceptor has been revisited and improved. This compound is a building block that is routinely synthesized by many research groups to be used in glycosylation refinement studies. This method provides consistent results and is superior to other strategies. Our studies culminated by the invention of 3,3-difluoroindolylthio (SFox) imidates. The synthesis and activation for glycosylation of these compounds has been studied. The SFox imidates showed high efficiency in 1,2-trans and 1,2-cis glycosylations.

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