Chemical Synthesis of Asparagine‐Linked Archaeal N‐Glycan from Methanothermus fervidus

Abstract

Several N-linked glycoproteins have been identified in archaea and there is growing evidence that the N-glycan is involved in survival and functioning of archaea in extreme conditions. Chemical synthesis of the archaeal N-glycans represents a crucial step towards understanding the putative function of protein glycosylation in archaea. Herein the first total synthesis of the archaeal L-asparagine linked hexasaccharide from Methanothermus fervidus is reported using a highly convergent [3+3] glycosylation approach in high overall yields. The synthesis relies on efficient preparation of regioselectively protected thioglycoside building blocks for orthogonal glycosylations and late stage N-aspartylation.

First Synthesis of Bacillus cereus Ch HF-PS Cell Wall Trisaccharide Repeating Unit

“…Glycosylation of 15 with 14 under TMSOTf activation using acetonitrile as a participating solvent at −40 °C cleanly afforded the β-linked product 16 ( 1 H NMR H-1 δ4.33, 13 C NMR C-1 δ 102.06) in 72% yield. Removal of the acetates under mild conditions (AcCl, MeOH, 94%) followed by benzylidene formation in acetonitrile as a solvent (90%) furnished 3-OH derivative 17 which was benzylated (92%) and subjected to a regioselective BH 3 -reductive ring opening reaction (80%) to fashion the requisite 6-OH acceptor 8 .…”

“One-Pot” Protection, Glycosylation, and Protection–Glycosylation Strategies of Carbohydrates

“…As introduced previously in Scheme , inverting the stereo configuration of a hydroxyl group via its transformation into a sulfonate, such as mesylate (OMs) and triflate (OTf), followed by nucleophilic S N 2 displacement, provides access to rare sugar or expensive building blocks, such as bacterial sugars or galactosamine derivatives . A few examples for stepwise conversion to galactosamine into protected derivatives have been reported by Toth, Ramström, − Bundle, Kulkarni , and Wang …”

“…The orthogonally protected rare sugar and glycosamine building blocks have been used in the assembly of various conjugation-ready bacterial oligosaccharides, including a trisaccharide fragment of Neisseria meningitides glycopeptide, a pseudotrisaccharide of Bacillus cereus, and phosphorylated trisaccharide of Providencia alcalifaciens O22, as well as archaeal N -linked hexasaccharide (Figure ). − ,, The azide containing rare sugars were shown to be especially useful for selective metabolic glycan labeling in pathogenic bacteria .…”

Total Synthesis of a Densely Functionalized Plesiomonas shigelloides Serotype 51 Aminoglycoside Trisaccharide Antigen

“…Azide reduction in 52 using the Staudinger conditions that had worked well for monosaccharide 15 failed to give desired trisaccharide amine 53 . Reduction of the azide in 52 using 1,3-propanedithiol and i Pr 2 NEt in MeOH gave an inseparable mixture of 2′′-dichloroacetamido-3′′-aminosugar 53 and the corresponding 2′′-trichloroacetamido-3′′-aminosugar. Notably, treatment of 52 with 1,3-propanedithiol, Et 3 N, and water in pyridine afforded pure 2′′-dichloroacetamido-3′′-aminosugar 53 .…”