Esterification of Salicylic acid with Succinylated Dextran Using ZrOCl₂.8H₂O over MCM-41: A Novel Strategy to Design Polysaccharide-Based Macromolecular Prodrugs

We are exploiting the use of a versatile catalyst taken from heterogeneous catalysis, i.e., ZrOCl₂.8H₂O to efficiently catalyze the reaction of dextran-succinate conjugate (Dex-SAn) with salicylic acid (SA) under homogeneous reaction conditions. Dextran was first linked with succinic anhydride using triethylamine as a base in DMAc to provide active functionalities (succinate moieties) situated away from the polymer chains. The resultant Dex-SAn conjugate was further esterified with SA using zirconium (IV) oxychloride octahydrate (ZrOCl₂.8H₂O) as a catalyst at 80 °C under N₂. Reaction conditions and amount of catalyst ZrOCl₂.8H₂O and chiral support MCM-41 were optimized. This reaction methodology resulted in macromolecular prodrugs of SA as Dex-SAn-SA conjugates in good yield. The structures of Dex-SAn and newly synthesized Dex-SAn-SA conjugates were characterized using various spectroscopic techniques, i.e., FT-IR, ¹H, and APT-¹³C NMR spectroscopy. The degree of substitution of SA on to Dex-SAn-SA was determined by UV/Vis spectroscopic methods. This reaction methodology can be modeled as a new protocol for facile attachment of several drug molecules onto the highly potential and biodegradable drug carrier dextran.