Synthesis of the polymethoxyflavones nobiletin, tangeretin, isosinensetin, and gardenin A–D

Abstract

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 A–D, are synthesized from this intermediate.