A stereoselective synthetic entry point to the 5–8–5 carbocyclic core of the ophiobolins was developed. This strategy exploits the chiral tertiary alcohol of ophiobolin A to guide assmebly of the 5–8–5 scaffold in a single step via a photoinitiated cycloisomerization. Mechanistic insights into the origin of stereocontrol in this reaction are described, as are efforts to elaborate the resultant fused 5–8–5 ring system to the pharmacophore of ophiobolin A.