Synthesis of triglycerides of phenylbutyric acids by lipase-catalyzed glycerolysis in a solvent-free system

Triphenylbutyrin, a triglyceride prodrug of 4-phenylbutyric acid, has potential for use in drug delivery systems. Immobilized Candida antarctica lipase B catalyzed the synthesis of triphenylbutyrin by glycerolysis of 4-phenylbutyrate with glycerol in a solvent-free system. The use of 4-phenylbutyate with a leaving alcohol moiety in the acyl-transfer reaction can shift the equilibrium of the reaction toward the synthesis of triphenylbutyrin, since the alcohol by-product can be removed by vacuum. A 97% yield of triphenylbutyrin was achieved in a solvent-free system at a reaction temperature of 75 °C by combination of molecular sieves to limit the hydrolysis side reaction and a vacuum system to shift the reaction equilibrium in a solvent-free system.