Chemospecific manipulations of a rigid polysaccharide: syntheses of novel chitosan derivatives with excellent solubility in common organic solvents by regioselective chemical modifications

Abstract

Efficient procedures for the preparations of soluble chitosan derivatives have been established on the basis of the regioselective chemical modifications. Selective and quantitative N-phthaloylation of chitosan proceeds smoothly by the reaction of chitosan with phthalic anhydride in N,N-dimethylformamide (DMF) at 130 C. The resulting phthaloylchitosan exhibits much improved solubility in common organic solvents such as DMF, NJV-dimethylacetamide, dimethyl sulfoxide, and pyridine. The enhanced solubility of new types of chitosan derivatives under homogeneous reaction conditions. Facile conversions of phthaloylchitosan, a key starting material, into several 6-0-substituted derivatives are carried out by the reactions with bulky substituents such as triphenylmethyl (trityl) and @-tolylsulfony1)oxy (tosyloxy) groups. These reactions also proceed in homogeneous solution under mild conditions, and the degrees of substitution are estimated to be 1.0. Subsequent 3-0-acetylation of the secondary hydroxyl groups of 6-0-substituted materials gives rise to regioselectively modified chitosan derivatives showing much better solubility. Specific N-dephthaloylation or 0-detritylation of 6-0-trityl derivatives affords versatile intermediates, which permit the introduction of additional functional groups regioselectively.