Studies of the Selective O-Alkylation and Dealkylation of Flavonoids. XXIV. A Convenient Method for Synthesizing 6- and 8-Methoxylated 5,7-Dihydroxyisoflavones.

Abstract

2', 4'-Bis(benzyloxy)-3', 6'-dimethoxychalcones (5), which were obtained from the dibenzyl ether of 2, 4-dihydroxy-3, 6-dimethoxyacetophenone (3), were oxidatively rearranged with thallium (III) nitrate in methanol and the resultant products were converted into 7-hydroxy-5, 8-dimethoxyisoflavones (8) by hydrogenolysis, followed by cyclization. The isoflavones were quantitatively demethylated to 5, 7-dihydroxy-8-methoxyisoflavones (2) via their acetates. The isomeric 5, 7-dihydroxy-6-methoxyisoflavones (1) were also synthesized from the chalcones, obtained from 2, 3-dimethoxy- (16) or 2-isopropoxy-3-methoxy-4, 6-bis(benzyloxy)acetophenones (21), by a similar method. On the other hand, the isoflavones with two hydroxy groups at the 2'- and 4'-positions were easily synthesized by the following method. Treatment of the rearranged product from 2, 2', 4, 4'-tetrakis(bezyloxy)-3', 6'-dimethoxychalcone (5f) with hydrochloric acid (HCl) in acetic acid afforded 2', 4', 7-tris(benzyloxy)-5, 8-dimethoxyisoflavone (10f). The 5-methoxy group in the isoflavone was quantitatively cleaved to give the corresponding 5-hydroxyisoflavone (11f), which was isomerized to 2', 4', 7-tris(benzyloxy)-5-hydroxy-6-methoxyisoflavone (25f) in the presence of anhydrous potassium carbonate. Hydrogenolysis of the two 5-hydroxyisoflavones proceeded smoothly to give 2', 4', 5, 7-tetrahydroxy-8-(2f) and 6-methoxyisoflavones(1f), respectively. The 13C-NMR spectra of these isoflavones supported the proposed structures of polyhydroxyisoflavones. The proposed structures of two natural isoflavones were revised.