On the Abundance and Stability of Diazo-Containing Secondary Metabolites: Enantioselective Synthesis of (-)-Nenestatin A.

Here, we report an enantioselective synthesis of the monomeric nes product (-)-nenestatin A, via the intermediary diazofluorene "diazonenestatin A." Our route features a convergent, aldol-based fragment coupling to assemble the carbon skeleton and a diazotransfer to a highly conjugated tetracyclic fulvene. We find that diazonenestatin A is transformed to nenestatin A under conditions that mimic the bacterial fermentation, suggesting that the nes pathway may produce unstable diazofluorene products that have eluded isolation.