Document Type

Dissertation

Degree

Doctor of Philosophy

Major

Chemistry, Organic

Date of Defense

8-5-2016

Graduate Advisor

Alexei V. Demchenko

Committee

Eike Bauer

Janet Braddock-Wilkings

James Chickos

Abstract

Glycosyl transfer within the active site of an enzyme involves the arrangement of the gly-cosyl donor and glycosyl acceptor in close proximity to each other. To mimic this pro-cess, intramolecular glycosylations are carried out where the donor and acceptor are linked together via a spacer. Correct orientation, rigidity and position of the spacer play a vital role in the selectivity and yield of reactions in this “molecular clamp method”. Though current methodologies show promising results in terms of yield and selectivity, the need to synthesize different complexes to ensure selectivities in all types of glycosidic linkages is a large deterrent to the wide spread use of this technique. Reported herein is a new molecular clamp method for the synthesis of oligomeric carbo-hydrates, based on a bis-phenol A (BPA) template, which allowed us to place the glyco-syl donor and acceptor counterparts in the correct orientation to each other using with dif-ferent length linkers (L1 and L2) for exceptional facial α-selectivity. This has been demonstrated in a majority of applications, particularly those involving glycosylation of the secondary glycosyl acceptors; exceptional selectivity for the synthesis of challenging α-linked disaccharides has been achieved. We have also demonstrated that a modified bis-phenol-A template allows for connection of multiple building blocks to perform in-tramolecular oligosaccharide synthesis.

Included in

Chemistry Commons

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