Total Syntheses of Biologically Active Pterocarpan, Isoflavan, and Isoflavanone from Dalbergia oliveri

Biological screening of the natural products from Dalbergia oliveri identified that (6aR,11aR)-3,8-dihydroxy-9-methoxypterocarpan and (3R)-7,2′-dihydroxy-4′,5′-dimethoxyisoflavanone significantly increased the proliferation of dermal papilla cells and subcutaneous injection of these compounds induced the anagen of hair cycle in animal models. These interesting biological activities led us to design a practical synthetic route to these natural products for further pharmacological evaluation. Here we report the first total syntheses of naturally occurring pterocarpan ((6aR,11aR)-3,8-dihydroxy-9-methoxypterocarpan), isoflavan ((3R)-5′-methoxyvestitol), and isoflavanone ((3R)-7,2′-dihydroxy-4′,5′-dimethoxyisoflavanone) in a racemic form. A mild ZnCl₂-mediated [3 + 2] annulation method was utilized with chromenes and 2-methoxy-1,4-benzoquinone to construct a pterocarpan framework in a one-pot manner. O-methylation and reductive cleavage of the benzylic C─O bond afforded 5′-methoxyvestitol, which was transformed to isoflavanone, 7,2′-dihydroxy-4′,5′-dimethoxyisoflavanone, via a three-step sequence including DDQ-mediated benzylic oxidation.