Making and Breaking of Glycosidic Bonds:From Glycosylation to Glycan Editing

Abstract

Carbohydrates, which are ubiquitously distributed throughout the three domains of life, play significant roles in a variety of vital biological processes. Access to unique and homogeneous carbohydrate materials is important to understand their physical properties, biological functions, and disease-related features. It is difficult to isolate carbohydrates in acceptable purity and amounts from natural sources. Therefore, complex saccharides with well-defined structures are often most conveniently accessed through chemical syntheses. Research in oligosaccharide synthesis encompasses both the discovery and development of formidable glycosylation methods and the invention of novel technologies that control regio- and stereo-chemical outcomes in each glycosidic bond formation. In this realm, gold-catalyzed glycosylation has emerged as a particularly intriguing and promising avenue for the construction of complex carbohydrate structures. Its success is largely due to the mild, catalytic, and highly reactive nature of the donor chemistry, along with the non-competitive leaving group. Over the past decade, many disaccharides, trisaccharides, and oligosaccharides have been efficiently generated using the distinctive advantages of gold-catalyzed donor chemistry. Within this framework, we have shown the effectiveness of a stable alkynyl glycosyl carbonate donor, as reported in 2016 by Mishra et al., in synthesizing complex glycan motifs found on the cell wall of Mycobacterium tuberculosis (pathogen causing the tuberculosis (Tb) disease). This highly efficient donor was used to synthesize the Arabinan 31-mer fragment, reminiscent of the Mycobacterium tuberculosis cell wall, using [Au]/[Ag]-catalysis. Additionally, we have explored the versatility of this alkynyl glycosyl carbonate donor in the domains of orthogonal and one-pot glycosylation strategies. Continuing our exploration of oligosaccharide synthesis, we aimed to develop innovative reaction strategies to tackle existing challenges in the synthesis of oligosaccharides and glycoconjugates. In this effort, we have successfully introduced a novel molecular one-potsurgical editing technique named CIStER (Cut-Insert Stitch-Editing Reaction sequence), specifically designed for precise glycan editing. This inventive technique expeditiously enables the creation of diverse oligosaccharides and glycan probes. Moreover, this innovative reaction technique was employed to create a novel transglycosylation strategy, enabling the formation of diverse classes of glycoconjugates and oligosaccharides from a single glycan unit.