New perspectives on the synthesis and function of septanose carbohydrates

Date of Completion

January 2005

Keywords

Chemistry, Biochemistry|Chemistry, Organic

Degree

Ph.D.

Abstract

Recently, the construction of expanded biopolymers---specifically oligodeoxynucleotides and oligopeptides---has gained considerable attention. These molecules are the result of a formal one carbon homologation of their respective monomers and have been shown to exhibit interesting biological activities. As an extension of this idea we have introduced a convenient and concise route towards the synthesis of septanose carbohydrate via carbohydrate based oxepines. Septanose carbohydrates are the result of a one-carbon homologation of pyranose carbohydrates and show promising results as future targets for structure-function probes in a variety of biological processes. ^ This manuscript outlines the synthesis, conformational analysis, and biological function of a number of septanose carbohydrates prepared from carbohydrate based oxepines. Our three step synthetic strategy towards the preparation of carbohydrate based oxepines is discussed in detail as previous routes towards the synthesis of septanose carbohydrates and carbohydrate based azepanes (a related ring expanded aza-sugar) are reviewed. The reactivity of carbohydrate based oxepines is analogous to glycal chemistry. Epoxidation of carbohydrate based oxepines using DMDO provides for 1,2-anhydroseptanoses that can serve as glycosyl donors in the preparation of septanose carbohydrates. ^ The conformational analysis of two methyl septanosides, prepared from a D-glucose based oxepine, has allowed for the assignment of the anomeric configuration of these molecules and the determination of their respective low energy conformations. This finding supports previous reports that monoseptanosides may reside in one dominant, low-energy conformation. The computational results are supported by experimental 1H NMR spectroscopic data and provide a tentative method for assigning the anomeric configuration for septanosides derived from carbohydrate based oxepines. ^ ITC and STD-NMR experiments show data that Concanavalin A binds methyl β-D-septanosides with modest affinity and in preference to methyl α-D-septanosides. Further, methyl β-D-septanosides are bound competitively with the natural α-pyranoside ligands. This is the first direct evidence for this class of ring expanded carbohydrates being bound by a natural protein. Preliminary results also show that several methyl septanosides and 1,2,3-triazole derivatives are able to bind α-glucosidase. ^

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