Improving Retinoic Acid Efficacy: Lipase‐Catalyzed Synthesis of Derivatives with Antiviral Activity

Abstract

An efficient enzymatic approach was applied to thesynthesis of new derivatives of retinoic acid. Nine derivatives, four ofthem new compounds, were obtained through lipase-catalysis withexcellent yield. In order to find the optimal reaction conditions, theinfluence of various parameters such as enzyme source,nucleophile:substrate ratio, enzyme:substrate ratio, solvent andtemperature was studied. The excellent results obtained by lipasecatalysis made the procedure very efficient considering theiradvantages such as mild reaction conditions and low environmentalimpact. In addition, several synthesized compounds exhibited lowercytotoxicity than the retinoic acid in Vero cells and a remarkably higherantiviral activity against Herpes simplex virus type 1 (HSV-1) andHerpes simplex virus type 2 (HSV-2).