Automated solution-phase multiplicative synthesis of complex glycans up to a 1,080-mer

Carbohydrates play essential roles in nature, such as in cell–cell communication, cell growth and immunoresponse. However, the synthesis of structurally well-defined carbohydrates, especially large-sized glycans, is a challenging task. Here we report an automated solution-phase multiplicative synthesis of complex glycans enabled by preactivation-based, multicomponent, one-pot glycosylation and continuous multiplying amplification. This was achieved by making a dual-mode automated solution-phase glycan synthesizer. Using this synthesizer, a library of oligosaccharides covering various glycoforms and glycosidic linkages was assembled rapidly, either in a general promoter-activation mode or in a light-induced-activation mode. The automated synthesis of a fully protected fondaparinux pentasaccharide (an anticoagulant) was realized on the gram scale. Furthermore, automated ten-component tandem reactions were performed, allowing the assembly of arabinans up to a 1,080-mer using this automated multiplicative synthesis strategy. The complexity of carbohydrate structures makes their synthesis challenging. Now, an automated glycan synthesizer is reported which is capable of preparing a library of bioactive oligosaccharides, including a fully protected fondaparinux pentasaccharide. Furthermore, the synthesizer can rapidly assemble arabinans up to 1,080-mer size, starting from monosaccharide building blocks.