Studies of the Selective O-Alkylation and Dealkylation of Flavonoids. XV. A Convenient Synthesis of 3,5,6-Trihydroxy-7-methoxyflavones and Revised Structures of Two Natural Flavones

Abstract

Abstract A mixture of 6-hydroxy-3,4′,5,7-tetramethoxy- and 5,6-dihydroxy-3,4′,7-trimethoxyflavone was converted into 6-acetoxy-5-hydroxy-3,4′,7-trimethoxyflavone by acetylation and following dealkylation. The 3-methoxyl group in the tosylate of the 5-hydroxyflavone was selectively cleaved with anhydrous aluminum bromide in acetonitrile to give 6-acetoxy-3-hydroxy-4′,7-dimethoxy-5-(tosyloxy)flavone. 3,6-Dihydroxy-4′,7-dimethoxy-5-(tosyloxy)flavone, a deacetylated product of the flavone, was easily hydrolyzed to the desired 3,5,6-trihydroxy-4′,7-dimethoxyflavone in high yield via the corresponding 6-methoxymethyl ether. Eight 3,5,6-trihydroxy-7-methoxyflavones were synthesized by this method and their properties were clarified. Additionally, two 3,5,8-trihydroxy-7-methoxyflavones were synthesized by a similar method and the structures of two natural flavones which were proposed as 3,5,6-trihydroxy-7-methoxyflavone derivatives were revised to be 4′,7-dimethoxy- and 3′,4′,7-trimethoxy-3,5,8-trihydroxyflavones.