Synthetic Studies Probing Elansolid Biosynthesis: A para‐Quinone‐Methide‐Triggered Intramolecular Diels–Alder Reaction

Abstract

The elansolids A1/A2 and B1–B3 are secondary metabolites formed by the gliding bacterium Chitinophaga sancti. They show antibacterial activity against Gram‐positive bacteria. It has been proposed that the biosynthesis of the tetrahydroindane unit involves an intramolecular Diels–Alder cycloaddition (IMDA). To study the biosynthetic proposal, the influence of an oxygen functionality at C‐20, the regiochemistry of the allylic alcohol precursor, and the nature of the phenol group were investigated. The oxygen functionality at C‐20 has a profound effect on the outcome of this reaction, resulting in a Prins‐type reaction cascade initiated by a p‐quinone methide intermediate, and leading to an unexpected cycloadduct. The corresponding 20‐deoxy precursor, as suggested for the naturally occurring IMDA precursor smoothly yields the desired IMDA product as a mixture of two endo products. These results support the hypothesis that nature probably uses an intramolecular Diels–Alder cycloaddition to generate the bicyclic core of the elansolids starting from a 20‐deoxygenated precursor.