Efficient synthesis of S-protected thiolated polysaccharide xylan

Since thiolated polysaccharides are valuable reactive carriers for thiol-ene reaction and thiol-disulfide exchange, we investigated a sophisticated method that avoids the crosslinking of thiols during polymer modification. Hydroxyl groups of xylan were activated by forming the phenylcarbonates and exploit as coupling group. The reactive xylan phenylcarbonates were allowed to react with the aminium chloride group under base addition to form the corresponding carbamate bond. The pKb of the base used was crucial for the successful synthesis. A pyridyl disulfide was applied as terminal functional moiety, which is not only a S -protected-but also an activated thiol for the synthesis of functional polysaccharide disulfides. The deprotected thiol, obtained by reduction of the disulfide, could be converted with a functional thiol. On the one hand, we have developed a valuable method to make disulfide chemistry easily accessible for the modification of neutral polysaccharides. On the other hand, the novel cationic polysaccharide derivative, where the functional group is bound by a reduction-sensitive disulfide bond, is an appealing product suitable for gene delivery applications.

Automated summary

In this study, we developed a method to avoid the crosslinking of thiols during polymer modification. Hydroxyl groups of xylan were activated to form phenylcarbonates and couple with aminium chloride group. We applied pyridyl disulfide as a terminal functional moiety to synthesize functional polysaccharide disulfides. The resulting cationic polysaccharide derivative is suitable for gene delivery applications.