The biomimetic synthesis and final structure determination of (+)- and (-)-centrolobine, naturally occurring diarylheptanoid 2,6-cis-disubstituted tetrahydro-2H-pyrans

Article abstract of DOI:10.1002/hlca.201000096

The enantiomerically pure title compounds were prepared by oxidative cyclization of their optically active diarylheptanoid precursors. The approach is considered as a biomimetic phenol oxidation via an intermediate quinone methide. The absolute configuration of the precursors is retained, and the transition state adopts the sterically most favorable diequatorial arrangement of the 2,6-substituents to afford the cis-configured natural products. The outcome unambiguously establishes the absolute configurations and the correlation with the chiroptical data. In addition, a problem of regioisomerism that had not been discussed before was solved, and the original assignment of the position of the MeO group in the natural centrolobines could be confirmed. As such the results are the experimental evidence for the corrections of long-term inconsistencies we had postulated in an earlier review article.