Université Paris-Saclay, CNRS, Institut de Chimie des Substances Naturelles, UPR 2301, 91198, Gif-sur-Yvette, France.
J Nat Prod. 2020 Oct 23;83(10):3069-3079. doi: 10.1021/acs.jnatprod.0c00636. Epub 2020 Oct 5.
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.
从 107 种新喀里多尼亚大戟科植物中提取了 292 种独特提取物，通过 LC-MS 进行了分析，并通过分子网络组织了代谢产物含量。基于这样一种假设，即分类群特异性分子更有可能具有结构新颖性，因此将分类数据映射到光谱网络上以检测属特异性聚类。通过这种方法，突出了一组独特于属的化合物。随后，对 的果实 EtOAc 提取物进行 MS 引导的纯化，分离得到了 13 种新的单内酯和“倍半萜”胡椒烷（-），以及已知的 tutin（）。通过高分辨质谱和 NMR 光谱数据分析阐明了新化合物的结构，并通过单晶 X 射线衍射分析确定了化合物 、 、 、 、 和 的绝对构型。通过化合物 的化学转化确定了化合物 和 的相对和绝对构型。该系列其他成员的绝对构型是基于生物发生考虑和相似符号和大小的特定旋光度来确定的。评估了化合物 - 对 HCT116 结肠、U87-MG 神经胶质瘤和 A549 肺癌人癌细胞系的抗增殖活性。在 C-2 位带有酰基链的化合物（即 、 、和 ）对三种所用细胞系的 IC 值均在微摩尔范围内。
