Total synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units

Abstract

Carbohydrates are diverse bio-macromolecules with highly complex structures that are involved in numerous biological processes. Well-defined carbohydrates obtained by chemical synthesis are essential to the understanding of their functions. However, synthesis of carbohydrates is greatly hampered by its insufficient efficiency. So far, assembly of long carbohydrate chains remains one of the most challenging tasks for synthetic chemists. Here we describe a highly efficient assembly of a 92-mer polysaccharide by the preactivation-based one-pot glycosylation protocol. Several linear and branched oligosaccharide/polysaccharide fragments ranging from 5-mer to 31-mer in length have been rapidly constructed in one-pot manner, which enables the first total synthesis of a biologically important mycobacterial arabinogalactan through a highly convergent [31+31+30] coupling reaction. Our results show that the preactivation-based one-pot glycosylation protocol may provide access to the construction of long and complicated carbohydrate chains.

Synthetic Glycans and Glycomimetics: A Promising Alternative to Natural Polysaccharides

“…For example, the approachw as developedf or the highly efficient synthesis of monosaccharide building blocks. [55] The automatedo ligosaccharide synthesizer [56] and the preactivation-based one-pot glycosylations trategy [57][58] have been actively utilized for the rapid assembly of defined oligo-or poly-saccharides. Chemoenzymatic synthesis, as an attractive and efficient methodf or the preparation of complex glycan molecules, has also received increasing attention.…”

Carbohydrate‐based vaccines for oncotherapy

“…44 With the strategy of oligosaccharide synthesis has greatly stepped forward in the last two decades, for instance, solid-phase synthesis, programmable chemoselective one-pot synthesis, preactivationbased one-pot synthesis, and chemo-enzymatic synthesis, all these innovations blaze avenues for the acquisition of pure and abundant TACAs. [45][46][47][48][49][50] One challenge is that most carbohydrate antigens are T-cell-independent antigens, which typically induce a weak immune response in the absence of external mediators. 145 As shown in Figure 2A, carbohydrate antigens activate B cells through reacting with the receptors on the surface of B cells, resulting in B cells to differentiate to plasma B cells.…”

Stereodirecting Effect of Cyclic Silyl Protecting Groups in Chemical Glycosylation

“…Furthermore, it is noteworthy that very recently this methodology was adopted in the synthesis of the 92-mer polysaccharide 113 in mycobacterial arabinogalactan, the structure of which contains eight -D-Araf linkages that are constructed with the 3,5-O-TIPDS-protected Araf donor 100 (Wu et al, 2017) (Fig. 16).…”