[ASAP] Isolation of Picrotoxanes from Austrobuxus carunculatus Using Taxonomy-Based Molecular Networking

4 years ago

[ASAP] Isolation of Picrotoxanes from Austrobuxus carunculatus Using Taxonomy-Based Molecular Networking

Florent Olivon, Pascal Retailleau, Sandy Desrat, David Touboul, Fanny Roussi, Cécile Apel, Marc Litaudon

A unique collection of 292 extracts from 107 New Caledonian Euphorbiaceae species sensu lato was profiled by LC-MS² 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 Austrobuxus was highlighted. The subsequent MS-guided purification of the fruit EtOAc extract of Austrobuxus carunculatus led to the isolation of 13 new monolactone and "norditerpene" picrotoxanes (2–14), along with the known tutin (1). The structures of the new compounds were elucidated by HRESIMS and NMR spectroscopic data analysis, and the absolute configurations of compounds 1, 3, 7, 11, 12, and 14 were determined by single-crystal X-ray diffraction analysis. The relative and absolute configurations of compounds 4 and 5 were ascertained by chemical transformation of compound 3. 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 1–14 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., 2, 4, and 13) showed IC₅₀ values in the micromolar range for the three cell lines used. The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jnatprod.0c00636. ¹H and ¹³C NMR chemical shifts of compound 1, X-ray analyses experimental details, ORTEP views, crystal data, structure refinement, and conventional hydrogen bonds of compounds 1, 3, 7, 9, and 11–14, ¹H, ¹³C, HSQC, HMBC, COSY, ROESY NMR spectra of compounds 1–4, 6, 9, and 11–14, ¹H, ¹³C of compounds 5, 8, and 10, ¹H, ¹³C, HMBC of compound 7, and HRESIMS data for compounds 1–14 (PDF) Crystallographic data (CIF) Crystallographic data (CIF) Crystallographic data (CIF) Crystallographic data (CIF) Crystallographic data (CIF) Crystallographic data (CIF) Crystallographic data (CIF) Crystallographic data (CIF) This article has not yet been cited by other publications.

Publisher URL: http://feedproxy.google.com/~r/acs/jnprdf/~3/gsBSMyH3rJ4/acs.jnatprod.0c00636

DOI: 10.1021/acs.jnatprod.0c00636