Asymmetric Total Syntheses of Hypoestin A, Albolic Acid, and Ceroplastol II.

The first asymmetric total synthesis of bioactive diterpenoid hypoestin A with an unprecedented [5-8-5-3] tetracyclic skeleton is accomplished in 15 steps from commercially available ( R )-limonene. Furthermore, the second asymmetric total syntheses of sesterterpenoids albolic acid and ceroplastol II in 21 steps are also reported. The synthetically challenging and highly functionalized [ X -8-5] ( X = 5 or 7) tricarbocyclic ring systems found in hypoestin A, albolic acid, ceroplastol II, and schindilactone A, as well as other natural products, are efficiently and directly constructed via a unique intramolecular Pauson-Khand reaction of an allene-yne. This work represents the first reported use of the Pauson-Khand reaction to access synthetically challenging eight-membered-ring systems in natural product synthesis.