Abstract
Hyperforin was isolated from western herb, St. John's wort (Hypericum perforatum). Hyperforin exhibits various biologic activities including mild anti-depressant activity, anti-malarial activity, inhibitory activity of human histone deacetylase, and CYP3A4 induction activity. And this compound has characteristic structure; highly substituted bicyclo[3.3.1]nonanone core, 4 asymmetric carbon center.
To synthesize attractive natural compound, hyperforin, our group developed the catalytic asymmetric Diels-Alder reaction. This key reaction gave substituted cyclohexene which has 2 contiguous asymmetric centers in high yield and selectivity (93% yield, 96% ee, exo: endo = >33: 1).
From this key intermediate, we already synthesized bicyclo core via Claisen rearrangement, intramolecular aldol cyclization as key intermediate.
And model study revealed that additional oxidation was possible using vinylogous Pummerer rearrangement.
