Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

Abstract

SummaryThe chemical synthesis of a series of mucin-type oligosaccharide fragments 1–7 containing an α-linked aminopropyl spacer ready for glycoarray attachment is reported. A highly convergent and stereoselective strategy that employs two different orthogonal protected galactosamine building blocks was used to access all of the targets. A tandem deprotection sequence, that did not require chromatography-based purification between steps, was employed to globally unmask all protecting groups and all final targets were isolated in good to excellent yields.

Chemo‐Enzymatic Synthesis of S. mansoni O‐Glycans and Their Evaluation as Ligands for C‐Type Lectin Receptors MGL, DC‐SIGN, and DC‐SIGNR

“…The benzyl protection was left untouched at this stage of the synthesis to aid in the separation of products by HPLC after enzymatic modifications. Deprotection of the N‐Troc functionality under standard conditions with LiOH or zinc/acetic acid amalgam failed to provide clean products but refluxing the compounds 9 and 10 in 1 m TBAF in THF afforded the clean S. mansoni core 11 in 95 % and the mucin core 2 trisaccharide 12 in 78 % yield after three steps …”

N-Heterocyclic Carbene Catalyzed Stereoselective Glycosylation of 2-Nitrogalactals

“…Notably, the nitro group of these compounds could be transformed to an N -acetylamino group smoothly (vide infra), offering valuable building blocks for O -glycopeptide synthesis. For example the mucin class of glycopetides, which contain an N -acetylaminogalactose motif and are α-linked to l -serine and l -threonine. ,, Furthermore, the successful reaction with l -threonine derivative indicated secondary alcohols are also suitable substrates for this methodology (see also 3u ). Additionally, reactions with 6- O -unprotected glycosyl acceptors bearing electron-donating or electron-withdrawing protecting groups afforded disaccharides 3r – t in moderate to good yields with excellent α-selectivities.…”

Stereoselective Glycosylation of 2-Nitrogalactals Catalyzed by a Bifunctional Organocatalyst

“…To showcase the methodology, the synthesis of mucin-type Core 6 and 7 glycoconjugates − 10 and 13 was attempted using the developed organocatalytic conditions (Scheme ). Starting from α-linked 2-nitrogalactoside 7d , selective silyl ether removal with TBAF afforded monohydroxylated 8 in 82% yield, ready to be glycosylated.…”