(+)‐Mannolide C is a complex hexacyclic C20 cephalotane‐type diterpenoid featuring a highly strained 7/6/6/5 tetracyclic core containing eight consecutive stereocenters and two bridging lactones. The first asymmetric total synthesis of (+)‐mannolide C has been accomplished by lipase‐mediated resolution, Ru‐complex‐catalyzed double ring‐closing metathesis (RCM) reactions, NiII‐catalyzed diastereoselective Michael addition, and MnIII‐catalyzed allylic oxidation as the key transformations.

+)-Mannolide C is a complex hexacyclic C 20 cephalotane-type diterpenoid featuring a highly strained 7/6/ 6/5 tetracyclic core containing eight consecutive stereocenters and two bridging lactones. The first asymmetric total synthesis of (+)-mannolide C has been accomplished by lipase-mediated resolution, Ru-complex-catalyzed double ring-closing metathesis (RCM) reactions, Ni II -catalyzed diastereoselective Michael addition, and Mn III -catalyzed allylic oxidation as the key transformations.