Chemical synthesis and tyrosinase-inhibitory activity of isotachioside and its related glycosides.

ABSTRACT

Isotachioside (1) and its related natural product 2 are isolated from Isotachis japonica and Protea neriifolia, respectively, and are categorized as analogs of arbutin (3), a tyrosinase inhibitor for practical use. Both of the natural products and several derivatives such as glucoside 4, xyloside 5, cellobioside 6, and maltoside 7 were synthesized via Schmidt glycosylation as a key step, and their tyrosinase inhibitory activity was evaluated. The half maximal inhibitory concentration (IC50) of 1-3 could not be determined even when the concentration was increased to 1000 µM. Contrastingly, glycosides 4-7, missing methyl and benzoyl groups, acted as tyrosinase inhibitors with IC50s of 417 µM, 852 µM, 623 µM, and 657 µM, respectively. Among these novel inhibitors, derivative 4 was the most potent, indicating that the structural combination of resorcinol and glucose was significant for inducing the inhibitory effect.