Total Synthesis of (±)-Dragmacidin E: Problems Solved and Lessons Learned.

(±)–Dragmacidin E was synthesized in 25 steps from commercially available 7-(benzyloxy)indole. Key transformations in this sponge metabolite’s preparation include (a) a Witkop cyclization to establish the bridging indole core, (b) cyclo-dehydrative pyrazinone formation to unite the two indole-bearing components, and (c) late-stage guanidine installation via chemoselective carbonyl activation.