Tetrahydroxanthones by Sequential Pd-Catalyzed C−O and C−C Bond Construction and Use in the Identification of the “Antiausterity” Pharmacophore of the Kigamicins

Readily available C-acylated cycloalkanones undergo efficient Pd catalyzed ring closure/cross-coupling providing 7-substituted tetrahydroxanthones in a single operation. One of the synthesized derivatives (depicted) is shown to selectively kill pancreatic cancer (PANC-1) cells under conditions of nutrient deprivation indicating that the tetrahydroxanthone is responsible, in part, for the "antiausterity" effects of the naturally occurring kigamicins.