Synthesis of 7,2 '-Dihydroxy-4 ',5 '-Dimethoxyisoflavanone, a Phytoestrogen with Derma Papilla Cell Proliferative Activity

This paper reports a concise and scalable method for the synthesis of the phytoestrogen 7,2 '-dihydroxy-4 ',5 '-dimethoxyisoflavanone 1 via an optimized synthetic route. Compound 1 was readily obtained in 11 steps and 11% overall yield on a gram scale from commercially available 3,4-dimethoxyphenol. The key features of the synthesis include the construction of the deoxybenzoin unit through a sequence of Claisen rearrangement, oxidative cleavage, and aryllithium addition and the efficient synthesis of the isoflavanone architecture from highly functionalized 2-hydroxyketone.