Constrained sialic acid donors enable selective synthesis of α-glycosides

Abstract

Sweet spot for making oligosaccharides Sugars pose a challenge for chemists: how to string together functional group–rich building blocks that can adopt multiple conformations. Two papers in this issue used sugar building blocks constrained by a macrocyclic linker to encourage formation of a specific glycosidic linkage (see the Perspective by Pohl). Ikuta et al. used glucose building blocks containing a linker that changes the sugar conformation to synthesize cyclic oligomers with only three or four units. The linker changes the conformation of the glucose monomers, enabling them to come together despite the strain in the final structure. Komura et al. prepared sialic acid building blocks with a linker that allows for selective formation of the α-anomeric linkage with a range of nucleophiles. They synthesized dimers of sialic acid with many different linkages and a pentamer with four α(2,8) linkages. This method enabled chemical synthesis of components of mammalian glycans involved in brain development, cell adhesion, and immune response. Science , this issue p. 674 , p. 677 ; see also p. 631