Total synthesis of marine secondary metabolite nafuredin B has been achieved for the first time using a convergent strategy. Sharpless epoxidation followed by acid catalyzed epoxide opening were adopted to install the tetrasubstituted hydroxy center, whereas the iterative Julia–Kocienski olefination, Wittig olefination and HWE olefination afforded the olefin bonds. Ring closing metathesis in the presence of a free tetrasubstituted hydroxy group provided the unsaturated δ-lactone moiety. This synthetic study provided unambiguous structural confirmation of the isolated nafuredin B.