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Access Type

WSU Access

Date of Award

1-1-2010

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Chemistry

First Advisor

DAVID CRICH

Abstract

This thesis describes investigations directed at the development of methods for the selenosulfide and disulfide rearrangements for the permanent functionalization of thiols, and in particular of cysteine and carbohydrate based thiols. Emphasis is placed on the newly invented silver mediated allylic desulfurative rearrangement for the primary modification of thiols and the synthesis of complex oligosaccharide mimics.

Chapter one introduces the concept of chemoselective ligations for the modification of macromolecules like carbohydrates and proteins. It overviews the native and non-native ligation techniques for their modification of such entities with a attention focusing on thiol based ligation techniques. The later part of chapter one describes the need for a permanent ligation technique for the thiol modification and draws attention to a novel method called the selenosulfide ligation.

The second chapter describes studies focused on the further development of the selenosulfide rearrangement through selenocyanate methodology. The synthesis of various selenocyanates as convenient synthons for the selenosulfide ligation is described. The successful application of this selenosulfide methodology to the synthesis of tertiary allyl sulfides in which cysteine containing small peptides were modified with lipid units is highlighted.

In the studies covered in chapter three, with the view to introducing farnesyl-like primary thio ether groups to cysteine peptides and electron deficient anomeric thiols, the allylic disulfide rearrangement was reassessed with the further goal of identifying phosphine-free reagents for the desulfurative rearrangement. This led to the invention of silver mediated allylic desulfurative rearrangement, which enabled the attachment of lipid groups to cysteine peptides and an anomeric thiol under mild reaction conditions. The protecting group-free synthesis of a glycoconjugate was accomplished using this methodology.

In chapter four, extending the concept of this novel metal mediated allylic desulfurative rearrangement as a chemoselective ligation technique, for the synthesis of complex oligosaccharides is described with a focus to the synthesis of β-(1,3)-glucan surrogates.

In chapter five, the experimental procedures and characterization data for the synthesized compounds are documented.