Eight-step synthesis of routiennocin

Routiennocin is a member of a family of polycyclic pyrrole ether antibiotics that simultaneously uncouple oxidative phosphorylation and inhibit ATPase as a result of selective complexation of divalent metal ions. We describe a concise synthesis of routiennocin with the longest linear sequence of 8 steps. Our synthesis features a unique bi-directional strategy, which entails a sequential ring-opening/cross metathesis of a highly strained cyclopropenone acetal. This approach enables rapid and highly convergent assembly of the fully extended polyketide subunit of this natural product from readily available homoallylic alcohol precursors.