Document Type

Dissertation

Degree

Doctor of Philosophy

Major

Chemistry

Date of Defense

8-7-2014

Graduate Advisor

Alexei Demchenko, PhD

Committee

Christopher D. Spilling, Ph.D.

James J. O’Brien, Ph.D.

Eike B. Bauer, Ph.D.

Abstract

Although scientists have been able to isolate certain classes of naturally occurring carbohydrates, the overall availability of pure natural isolates remains inadequate. As a result, chemical synthesis has been employed to access complex carbohydrates. Unfortunately, traditional oligosaccharide synthesis often requires laborious protecting-group manipulations that results in lower yields. Expeditious strategies effectively shorten the task of oligosaccharide assembly by minimizing the need for protecting-group manipulations between glycosylation steps, or even purification of the intermediates. Additionally, prediction of the stereoselective outcome of the coupling reaction between two sugar units is a major obstacle facing carbohydrate chemists. It is well known that 1,2-trans (β) glycosides can be easily obtained with the assistance of a neighboring participating group at C-2, typically an acyl moiety such as O-acetyl or O-benzoyl. In order to achieve 1,2-cis (α) glycosides, a glycosyl donor bearing a non-participating group at C-2 (e.g., O-benzyl, or azido) needs to be employed. Unfortunately, these reactions often proceed via SN1 mechanism and result in poor stereoselectivity. Presented herein is the investigation into the use of S-benzimidazolyl (SBiz) glycosides as building blocks for oligosaccharide synthesis. It has been determined that the SBiz leaving group can be manipulated to tune the reactivity of the building block. This reactivity of the leaving group can be significantly enhanced (or reduced) toward selective activation by the use of an N-protecting group on the imidazole ring. This, in turn, allows executing oligosaccharide assembly via the very effective active-latent concept and orthogonal activation-based strategies. Addressing the issue of stereocontrol of glycosylations, we report the use of silver(I) perchlorate (AgClO4) as a powerful promoter toward assembling 1,2-cis glycosides. In this study, AgClO4 is employed to promote glycosyl thioimidates as well as thioglycosides. Furthermore, we have investigated the use of various silver salts, such as AgBF4, AgPF6, AgOTf, and AgClO4 in the coupling reaction. Surprisingly, although the series of promoters all contain silver, their counter ions vastly affect the stereoselectivity of the product. AgClO4 was determined to induce a higher α to β ratio and in some cases this is a ten-fold increase.

OCLC Number

891656929

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