Isolation of Picrotoxanes from Using Taxonomy-Based Molecular Networking.

A unique collection of 292 extracts from 107 New Caledonian Euphorbiaceae species was profiled by LC-MS and the metabolite content organized by molecular networking. Based on the assumption that taxon-specific molecules are more likely to be structurally novel, taxonomic data were mapped on spectral networks to detect genus-specific clusters. Using this approach, a group of compounds unique to the genus was highlighted. The subsequent MS-guided purification of the fruit EtOAc extract of led to the isolation of 13 new monolactone and "norditerpene" picrotoxanes (-), along with the known tutin (). The structures of the new compounds were elucidated by HRESIMS and NMR spectroscopic data analysis, and the absolute configurations of compounds , , , , , and were determined by single-crystal X-ray diffraction analysis. The relative and absolute configurations of compounds and were ascertained by chemical transformation of compound . The absolute configurations of other members of the series have been proposed on the basis of biogenetic considerations and specific rotation values of similar sign and magnitude. Compounds - were evaluated for their antiproliferative activities against HCT116 colon, U87-MG glioblastoma, and A549 lung human cancer cell lines. Compounds bearing an acyl chain at C-2 (i.e., , , and ) showed IC values in the micromolar range for the three cell lines used.