Polysaccharides are the most abundant biopolymers on earth that serve various structural and modulatory functions. Pure, completely defined linear and branched polysaccharides are essential to understand carbohydrate structure and function.Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers. Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30-and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside. Quick access to polysaccharides provides the basis for future material science applications of carbohydrates.

A highly efficient TMSOTf-catalyzed HMDS silylation of sugars, which can easily be integrated with subsequent reactions in one-pot fashion, has been developed. Its usefulness was demonstrated by applications to streamlined regioselective one-pot protection and nonenzymatic acetylation of un-

Automated synthesis of DNA, RNA, and peptides provides quickly and reliably important tools for biomedical research. Automated glycan assembly (AGA) is significantly more challenging, as highly branched carbohydrates require strict regio- and stereocontrol during synthesis. A new AGA synthesizer enables rapid temperature adjustment from −40 to +100 °C to control glycosylations at low temperature and accelerates capping, protecting group removal, and glycan modifications using elevated temperatures. Thereby, the temporary protecting group portfolio is extended from two to four orthogonal groups that give rise to oligosaccharides with up to four branches. In addition, sulfated glycans and unprotected glycans can be prepared. The new design reduces the typical coupling cycles from 100 to 60 min while expanding the range of accessible glycans. The instrument drastically shortens and generalizes the synthesis of carbohydrates for use in biomedical and material science.