Phloretin-4-O-β-D-glucopyranoside (1), isolated from Homalium stenophyllum, was synthesized for the first time through aldol condensation and Schmidt glycosylation reactions aiming to develop a novel hydrophilic tyrosinase inhibitor. However, the specific rotation of synthetic 1 was found to be negative and different from that reported for natural product 1. Thus, L-glucoside 2 was chemically synthesized using the established synthetic route of 1, suggesting that the configuration of the natural product 1 was the same as that of 2, as their specific rotation and spectroscopic data were also the same. In addition, the evaluation of the inhibitory activity of 1 and 2 against tyrosinase indicated that 2 was 1.4 times more potent than 1, but they were both relatively weak. Therefore, the enantiomeric analogues 1 and 2 were proved to be unique tyrosinase inhibitors due to the chiral recognition from the tyrosinase active site.
Keywords: L-glucoside; Phloretin glycoside; Schmidt glycosylation; aldol reaction; tyrosinase inhibitor.