Synthesis of Clostridium bolteae Capsular Polysaccharide Fragments: A Repeating Disaccharide Unit

Abstract

Recent studies have shown a link between people with autism who have gastrointestinal disorders and the bacteria in their gut microflora. Clostridium bolteae has been isolated from stool samples of children with autism, and a surface capsular polysaccharide has been determined to have a repeating disaccharide unit comprised of rhamnose and mannose units: [→3)-α-D-Manp-(1→4)-β-D-Rhap-(1→]. However, D-rhamnose is an extremely rare sugar, and moreover sequencing of Clostridium bolteae did not show any of the enzymes necessary to biologically synthesize D-rhamnose. Therefore, this study is to confirm the absolute structure of this capsular polysaccharide. In this thesis the synthesis of a novel D-quinovose donor is described as well as its glycosylation with a mannose acceptor. Inversion at O-2 of the quinovose residue and subsequent glycosylation gave the D-rhamnose trisaccharide. Additionally, progress towards the L-rhamnose trisaccharide is described. The use of 2,3-O-carbonate or O-2 sulfonyl donors did not show β-selectivity. Inversion to L-quinovose was accomplished by a Lattrell-Dax inversion in low yields which should allow for a β-selective glycosylation.