Synthesis of fragments of a polysaccharide from Nocardia nova for structural and biological studies

Abstract

Nocardia are gram-positive bacteria. Nocardia nova is one of the Nocardia species and can cause serious disease, particularly in immunocompromised patients. Rapid diagnosis of N. nova can be lifesaving. The cell wall of N. nova contains an unusual glucose-modified arabinogalactan polysaccharide with a unique structure that may be a possible target for diagnostic development. In this thesis, I describe the synthesis of oligosaccharide fragments of the glucosyl-galactan domain of N. nova arabinogalactan. My targets are structures that contain one or two tetrasaccharide repeating units with an 8-azido-octyl linker at their reducing end. The approach I developed was to synthesize a key tetrasaccharide building block and then use it to glycosylate 8-azido-octanol. The same building block was used to carry out 4+4 glycosylation to obtain the octasaccharide. These molecules will be useful in confirming the structure of the polysaccharide, to generate monoclonal antibodies that could be used in a diagnostic, and to understand the immunological activity of this unique bacterial glycan.