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.