Synthesis of the Polymethoxyflavones Nobiletin, Tangeretin, Isosinensetin, and Gardenin A–D

We present a practical synthesis of 2’-hydroxy-3’,4’,5’,6’-tetramethoxyacetophenone, a multi-substituted benzene derivative, via CuCl-catalyzed Ullmann-type coupling reaction with MeONa. 2’-Hydroxy-3’,4’,5’,6’-tetramethoxyacetophenone is the key intermediate for the total synthesis of various polymethoxyflavones....