Biomimetic Total Synthesis of (±)-Verrubenzospirolactone

A five-step total synthesis of (+/-)-verrubenzospirolactone has been achieved using a biomimetic, intramolecular Diels-Alder reaction of a 2H-chromene to form two rings and four stereocenters in the final step. This Diels-Alder reaction occurs spontaneously at 30 degrees C on-water, and thus suggests that it is likely to be non-enzymatic in nature. The structure of (+/-)-verrubenzospirolactone was also used to inspire a quadruple cascade reaction to generate seven stereocenters, four rings, three C-C bonds, and two C-O bonds in one step.