Resorcinol alkyl glucosides as potent tyrosinase inhibitors

Resorcinol alkyl glucosides 7-12 were developed as novel tyrosinase inhibitors based on the structure of rhododendrin. These were synthesized from 2,4-dibenzyloxybenzaldehyde using either the Wittig or the Horner-Wadsworth-Emmons reaction with Koenigs-Knorr glycosylation as key steps. The tyrosinase inhibitory activity of 7-12 increased with the length of the alkyl spacer between resorcinol and glucose. The 50% inhibitory concentration (IC₅₀) of tetradecyl derivative 12 was 0.39 μM, making it the most potent of the compounds synthesized. The IC₅₀ of 8 (3.62 μM) with a propyl spacer was ca 10 times that of 7 (35.9 μM) with an ethyl spacer. This significant activity difference suggests that an interaction between resorcinol alkyl glucoside and tyrosinase may increase remarkably if the length of the alkyl spacer exceeds C₃.