Enantioselective Total Synthesis of (+)-Penostatins A and C

A stereoselective and column-economic approach to (+)-penostatins A and C has been developed. The multisubstituted A ring and B/C rings in their unique tricyclic framework are constructed through a Diels-Alder reaction/ozonolysis sequence and an exo intramolecular hetero-Diels-Alder reaction with high chemo-, regio-, and stereoselectivity. Using this route, (+)-penostatins A and C can be synthesized in 19 and 20 steps, respectively, with a good overall yield involving only five or six column chromatographic purifications.