A One-Pot, Two-Step Synthesis of Tetrahydro Asterriquinone E

Bis(indolyl)dihydroxyquinone 2, the tetrahydro analogue of naturally occurring 1a, was synthesized by a novel, expeditious route. The short synthesis was accomplished by treating p-bromanil (3) with 2 equiv of indole 4 in the presence of cesium carbonate in acetonitrile at ambient temperature to provide a 1:1 mixture of the dibromo regioisomers 7 and 8, followed by hydrolysis of the mixture to afford 2. The synthetic compound 2 was found to inhibit the binding of the Grb2 adapter protein to tyrosine-phosphorylated EGF receptor (IC50 = 1.2 μM).