We have achieved the first total synthesis of (-)-principinol C, which possesses an intriguing and complex 5/7/6/5 tetracyclic skeleton with eight contiguous stereocenters. The 5/7/6/5 tetracyclic skeleton of principinol C was assembled using an intramolecular Pauson-Khand reaction as the key step. This synthetic route represents the first application of the intramolecular Pauson-Khand reaction of enyne to construct the 7,5-bicyclic ring system in natural product synthesis.