Sugar Asymmetry: The Evolution of De Novo Asymmetric Syntheses of Carbohydrates from Hexoses to Oligosaccharides

Abstract

The ability to recognize hidden symmetry in a highly asymmetric world is a key factor in how we view and understand the world around us. Despite the fact that it is an intrinsic property of the natural world, we have an innate ability to find hidden symmetry in asymmetric objects. The inherent asymmetry of the natural world is a fundamental property built into its chemical building blocks (e.g., proteins, carbohydrates, etc.). This review highlights the role of asymmetry in the structure of the carbohydrates and how these stereochemical complexities present synthetic challenges. This survey starts with an overview of the role synthetic chemistry plays in the discovery of carbohydrates and their 3D structure. This review then introduces various de novo asymmetric synthetic approaches that have been developed for the synthesis of carbohydrates and, in particular, oligosaccharides. The two most successful strategies for oligosaccharide synthesis rely on diastereoselective palladium-catalyzed glycosylation. The first uses an Achmatowicz reaction to asymmetrically prepare pyranose building blocks along with a substrate-controlled Pd-glycosylation. The other strategy couples a ligand-controlled Pd-glycosylation with a ring-closing metathesis for oligosaccharide assembly.