The evolution of a program directed at the enantioselective total synthesis of maoecrystal V, a highly modified ent-kauranoid, is described. An early stage chiral auxiliary-directed asymmetric C-H functionalization for the construction of a key benzofuran intermediate enabled the first asymmetric synthesis of the natural enantiomer of maoecrystal V, confirming the assigned stereochemistry. A divergent course of the central intramolecular Diels-Alder reaction, which is dependent on the nature of the dienophile, initially led to the development of an unanticipated and previously unknown isomer of maoecrystal V, which we named maoecrystal ZG. In light of the reported selective and potent cytotoxic activity of maoecrystal V, the cytotoxic properties of maoecrystal ZG were also investigated.