Synthesis and absolute configuration of paraconiothin I, a structurally unique sesquiterpene isolated from the endophytic fungus Paraconiothyrium brasiliense ECN258

The total synthesis and determination of the absolute configuration are described for paraconiothin I, an inhibitor against the nuclear receptor liver X receptor alpha, which is produced by the endophytic fungus Paraconiothyrium brasiliense ECN258. Our method for synthesizing paraconiothin I involved Evans asymmetric alkylation and Sharpless asymmetric dihydroxylation, which enabled us to develop an efficient synthetic approach for constructing the side-chain moiety of paraconiothin I. Through model synthesis, we discovered that the previously proposed relative configuration of the natural product was incorrect and determined the correct absolute configuration of the natural product by comparing the specific rotations of the synthetic and natural products.