Synthesis of curdlan derivatives regioselectively modified at C-6: O-(N)-Acylated 6-amino-6-deoxycurdlan

• Highly regioselective bromination and azide displacement of curdlan at C-6.
• Chemoselective reduction of azidocurdlan to amine preserving ester moieties.
• In situ acylation during Staudinger reduction provides differentiated acyl groups.
• Pathway to regiochemically defined 6-amino- and 6-amido-6-deoxycurdlan derivatives.

There has been growing interest in aminopolysaccharide synthesis over the last two decades due to the critical natural functions of aminopolysaccharides, and their potential in biomedical applications. Regioselective introduction of amino groups into polysaccharide backbones is a challenge. Natural curdlan is a linear β-(1→3)-glucan that is of interest both for its physical properties and its biomedical applications. Aminated curdlan derivatives were synthesized in three steps. First, curdlan was regioselectively brominated at the C-6 position in lithium bromide-N,N-dimethylacetamide (DMAc/LiBr). Second, the bromide of the product 6-bromo-6-deoxycurdlan was displaced by nucleophilic substitution with sodium azide (NaN3) in dimethyl sulfoxide (DMSO). Third, O-acylated 6-amido-6-deoxycurdlan was produced by a one-pot method. 6-Azido-6-deoxycurdlan was subjected to Staudinger reduction, followed by reaction in situ with excess carboxylic anhydride, without isolation of the 6-amino-6-deoxycurdlan intermediate. Regioselectivity and degree of substitution (DS) of these derivatives were confirmed by 1H and 13C NMR spectroscopy, FTIR spectroscopy, and elemental analysis.