An alternative amine protection strategy for chitosan enabling chemoselective modifications

The trifluoroacetyl group is a widely used and easily removable amino-protecting group, making it an ideal choice for protecting the amino groups of chitosan. However, current methods for trifluoroacetylation of chitosan suffer from low reaction efficiency and limited modification degrees, posing a persistent challenge for achieving complete N-trifluoroacetylation. In this study, a simple and efficient method for preparing amino-protected chitosan, specifically N-trifluoroacetyl chitosan, is presented. The process is carried out in a homogeneous solution at room temperature, without the need for stringent anhydrous or oxygen-free conditions, and involves a brief reaction time. N-trifluoroacetyl chitosan exhibits good solubility in organic solvents, enabling homogeneous reactions with reagents such as enol ethers or t-butyldimethylchlorosilane. Furthermore, the protecting group can be easily removed under mild conditions. This method for amino group protection in chitosan offers a convenient approach for subsequent modifications.