Nature produces many molecules (so-called natural products) containing compact scaffolds such as cis-anti-cis-configurated 5/5/5 and 5/6/4 tricycles. But other molecules with more strained structures, such as trans-anti-cis-configurated 5/5/5 tricycles have been rarely found in nature. Accessing all these natural and non-natural molecules will strengthen the power of organic synthesis and benefit many fields such as medicinal chemistry, chemical biology that are heavily dependent on the available quantity of new/important molecules. Herein, we report a new strategy to synthesize molecules with cis-anti-cis-configurated 5/5/5 tricycles, 5/6/4 tricycles and trans-anti-cis-configurated 5/5/5 tricyclic skeletons by [5+2+1]/epoxidation/transannular radical cyclization strategy, where challenging cis and trans 5/8 bicycles with both ene and carbonyl functional groups were accessed by Rh-catalyzed [5+2+1] reaction of ene-vinylcyclopropanes and carbon monoxide, followed by epoxidation of the double bond in the 5/8 bicycles, and Ti(III) mediated epoxide/carbonyl cyclization to build target skeletons. This strategy was further applied to the first total synthesis of (+)-antrodiellin B, the asymmetric total synthesis of (−)-hypnophilin and formal synthesis of (−)-coriolin with cis-anti-cis configurated 5/5/5 skeleton (both hypnophilin and coriolin are highly oxidized and have significant biological activities).