Total Synthesis of Rubriflordilactone B

Abstract

Taking advantage of a 6π electrocyclization-aromatization strategy, we accomplished the first and asymmetric total synthesis of rubriflordilactone B, a heptacyclic Schisandraceae bisnortriterpenoid featuring a tetrasubstituted arene moiety. The left-hand fragment was accessed through a chiral-pool-based route, and linked to the right-hand fragment by a Sonogashira coupling. The cis geometry of the electrocyclization substrates was established by hydrogenation or hydrosilylation of the alkyne. An electrocyclization-aromatization sequence finally built the multisubstituted arene. The hydrosilylation approach was of significant advantage in terms of reaction scale, reproducibility, and intermediate stability. The structure of synthetic rubriflordilactone B was validated by X-ray crystallographic analysis, and found to be consistent with that reported for the authentic natural product based on an independent X-ray crystallographic analysis. However, obvious differences in the NMR spectra of the synthetic and authentic samples suggest that the authentic samples subjected to X-ray crystallography and NMR spectroscopy were two different compounds.

Keywords: arenes; electrocyclization; hydrosilylation; terpenoids; total synthesis.