Alginates are (1and4) linked linear copolysaccharides composed of B-D-mannuronic acid (M) and its C-5 epimer, a-L-guluronic acid (G). Several strategies to synthesize organically modified alginate derivatives have been reported, but almost all chemistries are performed in either aqueous or aqueous-organic media. The ability to react alginates homogeneously in organic solvents would open up access to a wide range of new chemistries and derivatives. However, past attempts have been restricted by the absence of methods for alginate dissolution in organic media. We therefore report a strategy to solubilize tetrabutylammonium (TBA) salts of alginic acid in polar aprotic solvents containing tetrabutylammonium fluoride (TBAF).

Acylation of TBA-alginate was performed in DMSO/TBAF to get products with DSacetyl up to ~ 1.0. We further report that by using appropriate solvent conditions, placement of acyl groups can be controlled to achieve either random or M-selective substitution. Alginate acetates synthesized in an M-selective fashion were used to study the ability of these derivatives to form Ca-crosslinked hydrogels. Detailed structure-property analyses were performed to identify acetylation reaction conditions and product properties that may be ideal for hydrogel formation. Furthermore, alginate esters were synthesized via modification of carboxylate groups on the backbone. These derivatives dissolved in polar aprotic solvents without the need to add TBAF. A proof of concept study showed their utility in the solubility enhancement of the poorly water soluble flavonoid naringenin.