Efficient synthesis of chitosan derivatives as clickable tools

An efficient method for the synthesis of a series of alkynoyl-chitosan derivatives having different properties is presented. Utilizing this method, we could introduce alkyne functionalities on the amino group of chitosan without the use of protection groups. We prepared two series of chitosan derivatives, one containing alkyl spacers which are soluble in organic medium while the other contains PEG spacers which have aqueous solubility. Furthermore, we could produce derivatives having varying degree of substitution on the chitosan backbone. This series of alkynoyl-chitosan derivatives would serve as a useful tool for linking other molecules through click chemistry and we have confirmed this by successfully performing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction with small and large azide molecules to produce four series of conjugates.