Unified Asymmetric Total Syntheses of (-)-Alotaketals A-D and (-)-Phorbaketal A.

The novel tricyclic spiroketal alotane-type sesterterpenoids showed strikingly different biological activities and potency with subtle structural alterations. Asymmetric total syntheses of the tricyclic sesterterpenoids (-)-alotaketals A-D and (-)-phorbaketal A were accomplished [29-31 steps from (-)-malic acid] in a collective way for the first time. The key features of the strategy included 1) a new cascade cyclization of vinyl epoxy δ-keto-alcohols to forge the common tricyclic spiroketal intermediate, 2) a late-stage allylic C-H oxidation, and 3) olefin cross-metathesis to install the different side chains.