Chemoselective modification of polysaccharides is a significant challenge, and regioselective modification is even more difficult, due to the low and similar reactivity of the various polysaccharide hydroxyl groups. Bromination of glycans that possess free 6-OH groups is exceptional in that regard, giving regiospecific, high-yield access to 6-bromo-6-deoxyglycans. Herein we report a simple and efficient pathway for synthesizing 6-ω-carboxyalkanamido-6-deoxy-containing polysaccharide derivatives in a sequence starting from 6-bromo-6-deoxycurdlan, via azide displacement, then conversion of the azide to the iminophosphorane ylide by triphenylphosphine (Ph3P). We take advantage of the nucleophilicity of the iminophosphorane nitrogen by subsequent regioselective ring-opening reactions of cyclic anhydrides. These reactions of the useful polysaccharide curdlan were essentially completely regio- and chemo-selective, proceeding under mild conditions in the presence of ester groups, yet preserving those groups. These interesting polysaccharide-based materials have pendant carboxyls attached through a hydrocarbon tether and hydrolytically stable amide linkage; as such they are promising for diverse application areas, including aqueous dispersions for coatings, adhesives, and other consumer products, and for amorphous solid dispersions in oral drug delivery.
Liu, S., Gao, C., Mosquera-Giraldo, L. I., Taylor, L. S., & Edgar, K. J. (2018). Selective synthesis of curdlan ω-carboxyamides by Staudinger ylide nucleophilic ring-opening. Carbohydrate Polymers, 190, 222–231. https://doi.org/10.1016/j.carbpol.2018.02.074