Synthesis of polymeric prodrugs of chlorphenesin with saccharide branches by chemo-enzymatic regioselective strategy

A facile and regioselective enzymatic synthesis approach to prepare polymerizable lipophilic chlorphenesin vinyl esters was developed in this research. The influence of different organic solvents, enzyme sources, reaction time and the acylation reagent on the synthesis of chlorphenesin vinyl esters was investigated. Then the polymerizable monomers 1-O-vinylsuccinyl-chlorphenesin (OVSC) and 1-O-vinyladipoyl-chlorphenesin (OVAC) were homopolymerized using AIBN as the initiator. The obtained polymeric prodrugs were characterized with IR, NMR and GPC analyzes. The poly-OVSC has Mn of 1.35 × 104 and Mw/Mn of 1.95, and the poly-OVAC has Mn of 2.37 × 104 and Mw/Mn of 4.30. Moreover, 6-O-vinyladipoyl-d-glucose (OVAG), a biocompatible monomer, was copolymerized with OVSC and OVAC. Polymeric prodrugs of chlorphenesin with saccharide branches were successfully obtained with high molecular weight.