A practical and economic route for regioselective cyclization of β-phenoxyl ynones to flavonoid derivatives†

Abstract

A green, efficient and highly regioselective synthesis of flavonoids and their derivatives from β-phenoxyl ynones using wet 1,3-propanediol as reaction medium was developed, without any metal catalysts, bases, acids or additives. The reaction shows a high level of functional tolerance and a broad substrate scope, with simple operation and high atomic economy. Furthermore, a mechanism study has shown that 1,3-propanediol acts both as a participant and solvent to achieve regioselective cyclization and carbonyl site oxygen migration. Significantly, the total synthesis of drug molecules efloxate 6 and flavodilol 7 and bioactive molecules, such as 8 and MN-64, further demonstrates the efficacy and synthetic potential of this method. Moreover, most established flavonoid derivatives are found to have strong anti-inflammatory activities, during which 2d exhibits a better result with lower IC₅₀ value of 5.67 μg mL⁻¹.