Straightforward Synthesis of C₂-Symmetric Ansaranes: Potential 3-D Structures to Mimic Naphthalene

A library of compounds possessing a rare 3-D pentacyclic skeleton known as ansarane has been prepared in high yields and only 3 steps. The sequence required at first the oxidation of salicylic alcohol with sodium periodate to deliver a spiroepoxyhexadienone, which spontaneously underwent, even at low temperature, a dimerization through a [4+2] cycloaddition. The trimeric adduct obtained in 86% was next irradiated at 350 nm to quantitatively furnish an ansarane. The C₂ symmetry of the molecule and the presence of two different electrophilic centers allowed a bidirectional approach through the regioselective ring-opening of the two epoxides by various nucleophiles (halogen, chalcogen, azido,…), or the olefination of the two keto groups. In parallel, the cyclic analogues of grandifloracin and grandifloridins, compounds reported for their biological properties against pancreatic cell lines, has been also prepared by a parent sequence. Finally, and on the basis of x-ray diffraction analysis, the 3D can be considered as a bioisostere of the naphthyl group.