Access Type

Open Access Dissertation

Date of Award

January 2011

Degree Type


Degree Name




First Advisor

David Crich


This dissertation consists of two parts of which the first develops the utility of α,β-unsaturated monothioanhydrides as a linchpins in multicomponent coupling reactions by processes involving addition to the double bond, cyclization onto the anhydride, and finally exploitation of the rich chemistry of the thioacid liberated in the cyclization. The second part of the thesis is concerned with verification of the structure of a nonprotein antifreeze oligosaccharide by the total synthesis of various authentic oligosaccharides and the comparison of spectroscopic data.

Chapter one starts with the introduction of the general characteristics and reactivity of thioacids, and their potential for application to the chemical synthesis of peptides and proteins. It continues with an overview of the solution and solid-phase synthesis of peptidyl thioacids and thioesters, and problems associated with them. Finally the chapter ends with an overview of cyclic thioanhydrides with emphasis on the potential for exploration of thiomaleic anhydride.

Chapter two of part one describes a series of multicomponent coupling reactions starting from thiomaleic anhydride. These processes begin either by Michael addition, radical addition, or cycloaddition onto the alkene and, following deprotection of a latent nucleophile in the adducts, continue with cylization onto the anhydride and concomitant liberation of a thioacid. Finally the thioacid is captured in a range of a amide or carbon carbon bond forming processes. In this manner a range of thiazines, benzothiazines, lactones, lactams, and oxazatricyclodecanes were prepared efficiently.

Chapter three extends a type of multicomponent coupling processes described in chapter two by the replacement of thiomaleic anhydride with various substituted thiitaconic anhydrides. To this end an efficient synthesis of substituted thioitaconic anhydride was first developed. Applying similar protocols to those developed with thiomaleic anhydride then enabled the synthesis of a range of thiazepines, benzothiazepins, and lactams.

The experimental procedures and characterization data for the all synthesized compounds discussed in part one of this dissertation are documented in chapter four.

Part two of this dissertation starts with chapter five which presents a brief overview of antifreeze substances before focusing on the ambiguous structure of a novel antifreeze oligosaccharide isolated recently from the Alaskan beetle Upis ceramboides. The chapter continues with an overview of a chemistry necessary for the synthesis of assorted oligosaccharides necessary for the verification of structure of the substance.

Chapter six opens with the retro synthetic analysis of mimics of the oligosaccharide by a convergent route before outlining the actual synthesis. Tetra, hexa, and octa saccharides corresponding to a proposed structure were synthesized along with tetrasaccharyl mimics of various possible linkage isomers. Extensive spectroscopic investigation of these oligosaccharides and comparison of the data with that of the natural isolate enabled the structure to be confirmed as [→4)-β-D-Manp-(1→4)-β-D-Xylp-(1→]n.

In chapter seven, the experimental procedures and characterization data for the synthesized compounds discussed in chapter five are documented, while in chapter eight the overall conclusions of the dissertation are presented.

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