The Total Synthesis of Dolabriferol: A retro-Claisen Approach from its Putative Precursor

Dolabriferol is a polypropionate natural product first isolated by Gavagnin and coworkers from the skin of the anaspidean mollusk, Dolabrifera dolabrifera. An unusual structural feature of dolabriferol is its noncontiguous carbon backbone that is proposed to arise via a retro-Claisen rearrangement of a cyclic hemiacetal precursor, perhaps as an artifact of isolation. Computational evaluations of the various cyclization/rearrangement manifolds available to the acyclic precursor have suggested that the pathway to dolabriferol from its linear precursor is plausible. The research presented herein describes the total synthesis of the putative precursor, evaluation of its properties, and a study of its retro-Claisen rearrangement. This study ultimately gave dolabriferol which suggests this compound may be formed during isolation; thus, the linear precursor (along with its tautomeric forms) is a plausible natural product. This is the first total synthesis of dolabriferol via its putative precursor