[Au]/[Ag]-Catalyzed Synthesis of Biologically Important Bacterial Oligosaccharides

Abstract

Oligosaccharides and glycoconjugates displayed on the cell wall of various living organisms and pathogens have a profound contribution to various cellular events such as host-guest interactions, cell signaling pathways, immune response etc. Understanding the structure and biological importance of the cell wall glycopolymers (CWG) enable researchers and industries to explore and leverage their potential for drug discovery in ways that would be challenging or impossible with natural sources because of the complex and heterogeneous abundance. Chemical synthesis of oligosaccharides through ‘glycosylation’ paves a pathway for obtaining homogeneous glycans in pure form, allowing for precise control over the types of linkages and attachments. Since 2006, the Hotha group has been dedicated to advancing glycosylation techniques and synthesizing complex oligosaccharides through their relentless efforts. Herein, we have extensively utilized the [Ag]-assisted [Au]-catalyzed mild activation method of alkynyl glycosyl carbonate donor in various facets of synthetic carbohydrate chemistry including total synthesis of complex bacterial cell wall glycopolymers and developed a new methodology for the synthesis of challenging 1,2-cis mannopyranosides. First, we have utilized the 4,6-benzylidine tethered 2-azido-2-deoxy mannopyranosyl carbonate donors in the synthesis of 1,2-cis glycoconjugates with broad substrate scope and a total synthesis of a trisaccharide motif from the cell wall of Streptococcus pneumoniae type 19F. Further, we have achieved the total synthesis of a conjugation ready hyperbranched pentasaccharide epitope of Clavibacter phaseoli in a [3+1+1] coupling strategy and via the application of nature inspired oxidation-reduction technique. Subsequently, we have extended our oligosaccharide syntheses efforts to the synthesis of a highly complex linear 38-mer galactofuran reminiscent of M. tubercusosis cell wall. The key oligosaccharide motifs including the linear tetradecasaccharide, repeating hexasaccharides, terminal octasaccharide and linker disaccharides were successfully synthesized in a highly convergent strategy.