Silylation of hyaluronan to improve hydrophobicity and reactivity for improved processing and derivatization

A novel hyaluronan (HA) derivative was synthesized through silylation reaction to improve the hydrophobicity of HA, to enhance its solubility in common organic solvents, and to make it more reactive for further derivatizations (e.g. esterification). While HA can not be silylated directly, its ion-paired complex with a long aliphatic chain quaternary ammonium salt (HA–CTA) was an effective starting material for the silylation reaction. The degree of silylation (DS) was controlled by changing the reaction parameters such as temperature, time and amount of silylation reagent. Silylated HA–CTA with a high DS (>3.2) was soluble in xylenes and hexane, while that with a low DS (3.2>DS>2.5) was only soluble in acetone, THF and 1,2-dichloroethane. The silyl groups and ammonium cations were also easily removed through hydrolysis to regenerate the native HA.