Bicubebin A, which was isolated from Aristolochia pubescens along with cubebin and cis-cubebin, contains six contiguous chiral centres and is the only reported lignan dimer containing this structural motif (fig 1). The synthesis of (-)-bicubebin A was designed to use the putative biological precursor, monomer (-)-cubebin. To explore this, cubebin was asymmetrically prepared in 12 steps. Successful dimerization of (-)-cubebin was then accomplished and yielded three bicubebins - (-)-bicubebin A, and two previously unreported bicubebins which were named (-)-bicubebin B and (+)-bicubebin C. The spectroscopic data for synthetic bicubebin A matched literature values, thus confirming the first synthesis of a lignan dimer of this type. Examination of spectroscopic data for bicubebin B found it was identical to that reported for the lactol cis-cubebin.Therefore the proposed lactol structure of cis-cubebin was synthesised (in 9 steps) and its data was found not match that reported in literature, thereby establishing that the isolated natural product was in fact a second dimer, bicubebin B.

Total synthesis of (-)-bicubebin A, (-)-bicubebin B and (+)-bicubebin C

256th National Meeting (2018)

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