Total Synthesis of Chalaniline A: An Aminofulvene Fused Chromone from Vorinostat-Treated Fungus <i>Chalara</i> sp. 6661

Chalaniline A, an aminofulveno[1,2-<i>b</i>]chromone derivative previously isolated from a vorinostat-treated ascomycete <i>Chalara</i> sp., was prepared in nine steps from orcinol (3,5-dihydroxytoluene). In a key transformation, the tricyclic ring system of the target was generated by a pyrrolidine-catalyzed double annulation between α-(methylsulfinyl)-2,6-dihydroxy-4-methylacetophenone and the ketaldoester, methyl 2,5-dioxopentanoate. The resulting tertiary alcohol (coniochaetone H) was further converted to chalaniline A by operations including dehydration (to yield a hydroxyfulvene), Vilsmeier reaction, and enamine exchange.