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. Subsequently, nobiletin, tangeretin, and gardenin AD, are synthesized from this intermediate.