Specific attachment of carbohydrates to the 2-amino functions of chitosan transforms this water-insoluble, linear polymer into branched-chain water-soluble derivatives. Facile conversions can be achieved by reductive alkylation using sodium cyanoborohydride and any aldehyde or keto sugar, by Schiff base formation, or by amidation reactions using carboxylic acid or lactone derivatives. Experimental results are presented for a series of mono-, di-, tri-, and polysaccharides, including D-glucose, IV-acetylglucosamine, D-glucosamine, D-galactose, D-galactosamine, D-fructose, D-glucoheptonic acid 7-lactone, lactose, cellobiose, maltose, melibiose, maltotriose, streptomycin sulfate, C6-o(de/iydo-cycloheptamylose, and dextran. These procedures facilitate the preparation of polymer derivatives with a variety of comblike, treelike, and other branching types. Many of these products are amenable to further, specific chemical modifications; this is demonstrated by the introduction, via galactose oxidase treatment, of C-6 aldehyde functions into the pendant galactose residues of derivatives 8 and 13. The synthetic chitosan derivatives exhibit a number of useful and uncommon properties in terms of their solution characteristics. Thus, aqueous solutions of derivative 8 were compatible with a wide range of salts, and derivatives 11 and 13 were stable in 50% aqueous ethanol. Derivative 8 formed inclusion complexes with iodine, lactose, and 4-oxo-2,2,6,6-tetramethylpiperidine-l-oxyl. Solubility modifications were accomplished by coreaction of hydrophilic (lactose) and hydrophobic (various alkyl) residues, affording products, such as 24, which were soluble in both aqueous and organic media. Reductive alkylation of chitin afforded the 1-deoxylactit-l-yl derivative 27, which was water insoluble but formed sols in water and several organic solvents. Factors affecting the solution behavior of chitosan and its branched derivatives have been evaluated and mechanisms have been discussed for solute interactions and conformational transitions.
