Synthesis and tyrosinase inhibitory activities of 4-oxobutanoate derivatives of carvacrol and thymol.

Carvacrol (1) and thymol (2) were converted to their alkyl 4-oxobutanoate derivatives (7-20) in three steps, and evaluated for tyrosinase inhibitory activity. The compounds showed structure-dependent activity, with all alkyl 4-oxobutanoates, except 7 and 20, showing better inhibitory activity than the precursor 4-oxobutanoic acids (5 and 6). In general, thymol derivatives exhibited a higher percent inhibitory activity than carvacrol derivatives at 500 μM. Derivatives containing three-carbon and four-carbon alkyl groups gave the strongest activity (carvacrol derivatives 9-12, IC50 = 128.8-244.1 μM; thymol derivatives 16-19, IC50 = 102.3-191.4 μM).