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

Abstract

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).