Automating Glycan Assembly in Solution

Abstract

Metrics & MoreArticle Recommendations S cientists' understanding of structure−function relationships 1,2 involving carbohydrates�one of the essential biomacromolecules in living systems�is not so detailed as those relating to DNA/RNA and proteins. Consequently, carbohydrates are far from widely used in the development of new therapeutics and diagnostics or in materials science. The bottlenecks hampering the growth of the field of glycoscience lie, not only in the lack of robust sequencing methods, but also in the difficulties associated with obtaining pure and well-defined glycans in adequate quantities from natural sources on account of their heterogenicity. While the chemical synthesis of glycans provides a promising solution to this conundrum, it represents a longstanding challenge for synthetic chemists, especially for those without a specialized knowledge of carbohydrate chemistry. Glycans can be linear or branched, and each glycosidic linkage is associated with a stereogenic center that requires perfect regioand diastereo-control during every coupling step in a synthesis. As a result, glycan synthesis 3 entails the skillful deployment of a bewildering array of protecting groups, extensive optimization of coupling conditions, and tedious separation of intermediates: all are time-consuming and labor-intensive.