A Practical and Economical High-Yielding, Six-Step Sequence Synthesis of a Flavone: Application to the Multigram-Scale Synthesis of Ladanein

Abstract

Herein we report a short and economic synthesis of the antiviral flavonoid lead ladanein (1). Ladanein is obtained from 2,6-dimethoxyquinone (11) in six steps with 51% overall yield. After a high-yielding reductive acetylation and Fries rearrangement, the flavone skeleton is built by means of a Baker–Venkataraman rearrangement. Throughout the synthetic pathway no chromatographic columns were used, and the reaction products were isolated and purified by optimized work-up and crystallization processes. This new process has been tested on a multigram-scale with an improved overall yield from 16 to 51% through six steps, and three chromatographic purifications used in the earlier synthesis were eliminated.