Wickerols A and B are diterpene natural products that have a novel fused 6−5−6−6 ring framework and exhibit potent antiviral activity against the H1N1 type A influenza virus. Herein, we report a divergent synthesis of wickerols A and B in 16 and 15 steps, respectively, from commercial sitolactone. The key reactions of the synthesis are a SmI 2 -mediated intramolecular ketone−allylic acetate reductive cyclization, a Claisen rearrangement, and an intramolecular alkylation/aldol reaction that rapidly assembled the compact tetracyclic core framework in a stereocontrolled manner. The work described herein allowed us to confirm the absolute configurations of wickerols A and B.

Sarocladione is the first 5,10:8,9-diseco-steroid with a 14-membered macrocyclic diketone framework to have been isolated from a natural source. Herein we report a biomimetic synthesis of sarocladione in only two or seven steps from inexpensive, commercially available ergosterol. The key feature of this synthesis was a novel ruthenium-catalyzed endoperoxide fragmentation, which transformed various saturated endoperoxides into olefinic diketones by cleavage of two C À C bonds. This synthesis allowed us to unambiguously determine the structure of sarocladione and provided experimental support for its revised biosynthetic origin. This work also vividly demonstrates that consideration of the biogenesis is a powerful tool for elucidating the structures of natural products.

Sarocladione is the first 5,10:8,9-diseco-steroid with a 14-membered macrocyclic diketone framework to have been isolated from a natural source. Herein we report a biomimetic synthesis of sarocladione in only two or seven steps from inexpensive, commercially available ergosterol. The key feature of this synthesis was a novel ruthenium-catalyzed endoperoxide fragmentation, which transformed various saturated endoperoxides into olefinic diketones by cleavage of two C À C bonds. This synthesis allowed us to unambiguously determine the structure of sarocladione and provided experimental support for its revised biosynthetic origin. This work also vividly demonstrates that consideration of the biogenesis is a powerful tool for elucidating the structures of natural products.