Synthesis of tyrosinase inhibitory kojic acid derivative

Abstract

Kojic acid derivative 2 was synthesized by joining two pyrone rings through an ethylene linkage by Horner-Emmons reaction of phosphonate 6 with aldehyde 7. The intermediates 6 and 7 were derived from kojic acid. The tyrosinase inhibitory activity of 2 was about 8 times more potent (IC50 = 3.63 mu M) than that of kojic acid (IC50 = 30.61 mu M). Compound 2 also exhibited potent melanin synthesis inhibitory activity (19.53% inhibition at 5 mu g) indicating that the connection of two pyrone rings of kojic acid through a suitable linker can be an useful strategy for identification of potent tyrosinase inhibitiors.