Regioselective and Scalable Total Synthesis of Licochalcone C and Related Licoagrochalcones

A novel efficient method for the synthesis of licochalcone C in good yield on up to 30 g scale was developed. The reaction sequence included relied on the directed ortho-metalation (DOM) of bis-O-MOM-protected resorcinol for the regioselective C-prenylation, followed by metalation-formylation, selective O-deprotection of a hydroxyl group located between the formyl and prenyl groups, its methylation, and aldol reaction with p-hydroxyacetophenone. Synthesis of structurally related retrochalcones, i.e., licoagrochalcones B, C, and D, was also proposed.

Automated summary

A new and efficient method for synthesizing licochalcone C in good yield has been developed, involving directed ortho-metalation for regioselective C-prenylation, metalation-formylation, selective O-deprotection, methylation, and aldol reaction. The synthesis of structurally related retrochalcones licoagrochalcones B, C, and D was also proposed.