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

摘要

Biological screening of the natural products from Dalbergia oliveri identified that (6aR,11aR)-3,8-dihy-droxy-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 ana-gen 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 race-mic form. A mild ZnCl2-mediated [3 + 2] annulation method was utilized with chromenes and 2-meth-oxy-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.