Chemists smash record for longest polysaccharide

Hooking sugar molecules together to make strings called glycans—also known as oligosaccharides and polysaccharides—is one of synthetic chemistry’s most bedeviling challenges. Carbohydrates are intrinsically complex and finicky reactants. Chemists led by Peking University’s Xin-Shan Ye report an automated solution-​phase synthesizer that can hook up sugars to make polysaccharides of record-breaking length and bioactive oligosaccharides that could be used as drugs (Nat. Synth. 2022, DOI: 10.1038/s44160-022-00171-9). Using the device, Ye’s team created a polysaccharide composed of 1,080 sugar moieties with 4,320 stereogenic centers, which is the longest and largest synthesized to date. The researchers also used the system to build a version of the pentasaccharide drug fondaparinux, an anticoagulant that has historically been tough to make at large scale. Ye and colleagues were able to prepare more than a gram of a fondaparinux precursor that includes protecting groups. “This automated platform will not only benefit nonspecialists, who will be able to assemble target glycans, but can also be applied to the streamlined synthesis of other organic molecules of interest,” the researchers write in the paper.