In summary, we examined a new synthetic approach to the central framework of ophiobolin A (1). As part of this process, we established a strategy for the stereocontrolled assembly of 5-8-5 ring systems that is concise, modular, and amenable to asymmetric induction. This molecular framework is central to the fusicoccanes, ophiobolanes and bipolarolides. As such, this chemistry harbors utility beyond the specific context presented here. As evidenced by an 8-step synthesis of intermediate 24, our approach allows for the controlled installation of peripheral groups around polycycle 12. Although the envisioned late-stage rearrangement of epoxide 24 was thwarted by an undesired fragmentation pathway, we postulate that the strategy presented here can be adapted to prepare the ophiobolins and related nonnatural compositions of matter. Research along these lines is underway and will be reported in due course.