Title

Carbohydrate based oxepines: Preparation and utilization for the synthesis of septanose glycoconjugates

Date of Completion

January 2008

Keywords

Chemistry, Biochemistry|Chemistry, Organic

Degree

Ph.D.

Abstract

A better understanding of the role of carbohydrates in biological processes has encouraged the development of analogues that can serve as tools for glycobiology. Septanose carbohydrates are ring-expanded analogues of pyranose carbohydrates that are defined by having a seven-membered ring. They have never been isolated in Nature. Interest in septanoses comes from the desire to understand their conformational features and to ascertain if these features will elicit a response from naturally occurring biological systems. The synthesis of septanose carbohydrates, however, has been relatively unexplored. This manuscript delineates the synthesis and biochemical characterization of a number of novel septanose carbohydrates. ^ Carbohydrate-based oxepines have been central to the preparation of septanose carbohydrates. Chapter one discusses the synthesis of these oxepine systems. A five-step preparation of carbohydrate-based oxepines by the sequential cyclization-elimination of hydroxy acetals is described. Also outlined is the ring expansion of gamma lactones to provide oxepinone systems. These systems have been shown to be viable precursors for the formation of oxepines by action of reducing agents. ^ Chapter two outlines the transformation from oxepine to septanose carbohydrate. Synthetic pathways that allow for the generation of oxepane carbohydrates are reviewed. S-phenyl septanoside donors are introduced and their uses in the preparation of a series of α-D-idoseptanosyl glycosides are described. ^ A number of biologically important associations are mediated by protein–carbohydrate interactions. In chapter three we answer the question, "Can an unnatural septanose sugar be bound by a natural protein?" The recognition of septanose carbohydrates by concanavalin A and the synthesis of substituted septanosyl-1,2,3-triazoles as potential glycosidase inhibitors are examined. ^