A Pericyclic Reaction Cascade in Leporin Biosynthesis
All roads lead to Rome: The biosynthesis of the leporins in Aspergillus sp. involves an unprecedented pericyclic reaction cascade. The enzyme LepI directs the periselectivity of a [4+2] cycloaddition towards a hetero‐Diels–Alder reaction outcome to give the leporin molecular scaffold. The Diels–Alder side product is morphed into the leporin core structure by a LepI‐catalyzed retro‐Claisen rearrangement, culminating in efficient kinetic side product recycling.