Glycan Assembly Strategy: From Concept to Application

Abstract

Glycans have been hot topics in recent years due to their exhibition of numerous biological activities. However, the heterogeneity of their natural source and the complexity of their chemical synthesis impede the progress in their biological research. Thus, the development of glycan assembly strategies to acquire plenty of structurally well‐defined glycans is an important issue in carbohydrate chemistry. In this review, the latest advances in glycan assembly strategies from concepts to their applications in carbohydrate synthesis, including chemical and enzymatic/chemo‐enzymatic approaches, as well as solution‐phase and solid‐phase/tag‐assisted synthesis, are summarized. Furthermore, the automated glycan assembly techniques are also outlined.

VaporSPOT: Parallel Synthesis of Oligosaccharides on Membranes

“…For successful glycosylations, two main parameters had to be optimized: the temperature inside the glycosylation chamber and the amount and concentration of the activator solution to be delivered. Both affect the reactivity of the building blocks and the yield. − For the preparation of different oligosaccharides, 14 building blocks (BBs, Figure ) were either synthesized following established protocols ,− or prepared from commercially available precursors (trichloroacetimidates 3 , 5 , and 9 and phosphates 6 and 8 , see Section B in the Supporting Information). To optimize the coupling conditions, glycosyl donors 1 – 6 and 8 – 12 were screened, using 8% TMSOTf in dichloromethane (Figure A), to furnish the corresponding dimers 15 – 17 in different yields (Figure B).…”

“…Despite their relevance in many processes of life, their role is still not sufficiently understood. , Their structural heterogeneity, complexity, and diversity often make their isolation from natural sources laborious and their synthesis a cumbersome process. Therefore, different automated platforms for enzymatic, − chemoenzymatic, , and chemical oligosaccharide − synthesis have been developed, giving access to complex and biologically valuable structures. − In the last two decades, the development of automated glycan assembly (AGA) has enabled the successful synthesis of defined and complex synthetic oligosaccharide libraries of biological and medical interest, ,− as well as very long polysaccharides including complex branching, up to 100-mers. , Currently, AGA is used to prepare one single oligosaccharide at a time. Parallel oligosaccharide synthesis would be more cost- and time-efficient.…”

Donor Preactivation-Based Glycan Assembly: from Manual to Automated Synthesis

“…The advantages of this strategy include the following: (1) obtaining unique chemoselectivity after preactivation to facilitate the regioselective and stereoselective construction of glycosidic bonds; (2) glycosyl donor reactivity independence allowing coupling reactions involving low-reactivity donors; (3) enabling multiple-step glycosylations without the need for intermediate purification; and (4) only requiring stoichiometric building blocks without complex protecting group manipulations. Over the past 20 years, this strategy has become a powerful tool for glycan synthesis as witnessed by the elegant assembly of many complex glycans and glycoconjugates such as tumor-associated carbohydrate antigens, various glycosaminoglycans, complex N -glycans, and diverse bacterial glycans. ,− In this Account, we report our achievements in the development and applications of the donor preactivation-based one-pot glycosylation strategy, a streamlined solution-phase synthesis strategy, aiming to accelerate oligosaccharide and polysaccharide synthesis from manual to automated synthesis.…”

Orthogonal Deprotection of Photolabile Protecting Groups and Its Application in Oligosaccharide Synthesis

“…A major obstacle is the difficulty of accessing a sufficient number of structurally well-defined glycans. 2 Chemical synthesis is a reliable way to solve this bottleneck problem, and a series of glycosylation methods, synthetic strategies, and purification methods have been reported to streamline the preparation of saccharides. 3−5 Carbohydrates are compounds with multiple hydroxyl groups; thus, protecting groups are necessary for the feasible chemical synthesis of complex saccharides.…”

“…Although glycoscience has received unprecedented attention in recent decades, it still lags behind polypeptides and nucleic acids. A major obstacle is the difficulty of accessing a sufficient number of structurally well-defined glycans . Chemical synthesis is a reliable way to solve this bottleneck problem, and a series of glycosylation methods, synthetic strategies, and purification methods have been reported to streamline the preparation of saccharides. − Carbohydrates are compounds with multiple hydroxyl groups; thus, protecting groups are necessary for the feasible chemical synthesis of complex saccharides. , Protecting groups not only enable regioselective glycosylation but also direct the stereoselectivity of glycosylation reactions and even have an influence on the activities of glycosyl donors or acceptors .…”