Bioactive polysaccharides from natural resources target various biological processes and are increasingly used as potential target molecules for drug development. However, the accessibility of branched and long complex polysaccharide active domains with well-defined structures remains a major challenge. Herein we describe an efficient first total synthesis of a highly branched heptadecasaccharide moiety of the native bioactive galectin-3-targeting polysaccharide from Carthamus tinctorius L. as well as shorter fragments of the heptadecasaccharide. The key feature of the approach is that a photo-assisted convergent [6+4+7] one-pot coupling strategy enables rapid assembly of the heptadecasaccharide, whereby a photoremovable o-nitrobenzyl protecting group is used to generate the corresponding acceptor for glycosylation in situ upon ultraviolet radiation. Biological activity tests suggest that the heptadecasaccharide can target galectin-3 and inhibit pancreatic cancer cell growth.
The first total synthesis of Haemophilus ducreyi lipooligosaccharide core octasaccharides containing natural and
unnatural sialic acids has been achieved by an efficient chemoenzymatic
approach. A highly convergent [3 + 3] coupling strategy was developed
to chemically assemble a unique hexasaccharide bearing multiple rare
higher-carbon sugars d-glycero-d-manno-heptose (d,d-Hep), l-glycero-d-manno-heptose
(l,d-Hep), and 3-deoxy-α-d-manno-oct-2-ulosonic
acid (Kdo). Key features include sequential one-pot glycosylations
for oligosaccharide assembly and the construction of the challenging
α-(1 → 5)-linked Hep–Kdo glycosidic bond by gold-catalyzed
glycosylation with a glycosyl ortho-alkynylbenzoate
donor. Furthermore, the sequential enzyme-catalyzed regio- and stereoselective
introduction of a galactose residue using β-1,4-galactosyltransferase
and different sialic acids using a one-pot multienzyme sialylation
system was efficiently accomplished to provide the target octasaccharides.
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