Antrodiellin B/hypnophilin/coriolin and strained 5/5/5 and 5/6/4 skeletons via [5+2+1]/epoxidation/transannular radical cyclization

Many natural products contain compact cis-anti-cis-configurated 5/5/5 and 5/6/4 tricycles, and efficient access to these molecules is posing many hurdles to the synthetic community. Accessing molecules with more strained trans-anti-cis-configurated 5/5/5 tricycles (which are rarely found in nature) was envisioned to be more challenging, and no solution to this has been reported. We describe here a [5+2+1]/epoxidation/transannular radical cyclization strategy to solve the above-mentioned challenges, as demonstrated by the first total synthesis of (+)-antrodiellin B, the asymmetric total synthesis of (−)-hypnophilin, and the formal synthesis of (−)-coriolin, all of which contain a cis-anti-cis-configurated 5/5/5 skeleton, together with the synthesis of compounds with 5/6/4 and trans-anti-cis-configurated 5/5/5 tricycles. The present strategy is helpful for obtaining these and other molecules and their analogs for future downstream studies dependent on synthetic molecules with unusual scaffolds.