Mathioudaki Angeliki, Berzesta Ariola, Kypriotakis Zacharias, Skaltsa Helen, Heilmann Jörg
Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, 157 71, Athens, Greece; Universität Regensburg, Pharmaceutical Biology, Universitätsstr. 31, D-93053, Regensburg, Germany.
Technological Education Institute, School of Agricultural Production, Lab. of Taxonomy and Management of Wild Flora, Stavromenos P.O.Box 140, Heraklion-Crete, 71110, Greece.
Phytochemistry. 2018 Feb;146:1-7. doi: 10.1016/j.phytochem.2017.11.009. Epub 2017 Dec 22.
Thirteen compounds were isolated from the aerial parts of Hypericum kelleri Bald., growing as an endemic on the island of Crete (Greece). These compounds comprise four previously unknown prenylated xanthones 1,2-dihydro-3,8-dihydroxy-6-methoxy-1,1,5-tri(3-methylbut-2-enyl)xanthen-2,9-dione (kellerine A), 1,2-dihydro-3,6,8-trihydroxy-1,1,5-tri(3-methylbut-2-enyl)xanthen-2,9-dione (kellerine B), 1,2-dihydro-3,8-dihydroxy-6-methoxy-1,1-bi(3-methylbut-2-enyl)xanthen-2,9-dione (6-methylpatulone), (R/S)-1,3,5-trihydroxy-2-(3-methyl-2-buten-1-yl)-4-[2-(3-methylbut-2-enyl)-3-methylbut-3-enyl]-6-methoxy-9H-xanthen-9-one ((2″R/S)-kellerine C) and the hitherto undescribed depsidone (R/S)-1,3,6-trihydroxy-5-methoxy-2-(3-methyl-2-buten-1-yl)-4-[2-(3-methylbut-2-enyl)-3-methylbut-3-enyl]-11Η-dibenzo[b,e] [1,4]dioxepin-9-one ((2″R/S)-creticine). As known compounds, brevipsidone D, 4-geranyl-2-(2'-isobutyryl)-phloroglucinol, 4-geranyl-2-(2'-methylbutyryl)-phloroglucinol, I3, II8-biapigenin, quercetin, avicularin, pseudohypericin and neochlorogenic acid have been isolated. The structures were elucidated on the basis of their 1D, 2D NMR, CD and MS data. The study confirms the typical occurrence of xanthones in Hypericum section Oligostema (Boiss.) Stef., and is also the first report on the simultaneous isolation of acylphloroglucinols in this section. Furthermore the first evidence of depsidones in the genus Hypericum L. is reported. Cytotoxicity was investigated in HeLa cells for prenylated xanthones and the depsidones. Both triprenylated 1,2-dihydroxanthones (kellerine A and B) showed significant in vitro cytotoxicity with IC values of 2.5 ± 0.1 (kellerine A) and 5.9 ± 0.9 (kellerine B) μM, whereas other compounds were less cytotoxic (IC > 20 μM).
从克里特岛（希腊）特有的克氏金丝桃（Hypericum kelleri Bald.）地上部分分离出13种化合物。这些化合物包括4种前所未知的异戊烯基呫吨酮：1,2 - 二氢 - 3,8 - 二羟基 - 6 - 甲氧基 - 1,1,5 - 三（3 - 甲基丁 - 2 - 烯基）呫吨 - 2,9 - 二酮（凯勒林A）、1,2 - 二氢 - 3,6,8 - 三羟基 - 1,1,5 - 三（3 - 甲基丁 - 2 - 烯基）呫吨 - 2,9 - 二酮（凯勒林B）、1,2 - 二氢 - 3,8 - 二羟基 - 6 - 甲氧基 - 1,1 - 二（3 - 甲基丁 - 2 - 烯基）呫吨 - 2,9 - 二酮（6 - 甲基帕图洛酮）、（R/S）-1,3,5 - 三羟基 - 2 - （3 - 甲基 - 2 -丁烯 - 1 - 基）-4 - [2 - （3 - 甲基丁 - 2 - 烯基）-3 - 甲基丁 - 3 - 烯基]-6 - 甲氧基 - 9H - 呫吨 - 9 - 酮（（2″R/S）-凯勒林C）以及迄今未描述的缩酚酸酮（R/S）-1,3,6 - 三羟基 - 5 - 甲氧基 - 2 - （3 - 甲基 - 2 - 丁烯 - 1 - 基）-4 - [2 - （3 - 甲基丁 - 2 - 烯基）-3 - 甲基丁 - 3 - 烯基]-11Η - 二苯并[b,e][1,4]二氧杂环庚英 - 9 - 酮（（2″R/S）-克里特辛）。作为已知化合物，短缩酚酸酮D、4 - 香叶基 - 2 - （2'-异丁酰基）-间苯三酚、4 - 香叶基 - 2 - （2'-甲基丁酰基）-间苯三酚、I3, II8 - 双芹菜素、槲皮素, 扁蓄苷、假金丝桃素和新绿原酸已被分离出来。根据它们的一维、二维核磁共振、圆二色光谱和质谱数据阐明了其结构。该研究证实了呫吨酮在金丝桃属少蕊组（Boiss.）Stef.中的典型存在，也是该组中同时分离出酰基间苯三酚的首次报道。此外，还报道了金丝桃属中缩酚酸酮的首个证据。对异戊烯基呫吨酮和缩酚酸酮在HeLa细胞中进行了细胞毒性研究。两种三异戊烯基化的1,2 - 二氢呫吨酮（凯勒林A和B）在体外均表现出显著的细胞毒性，IC值分别为2.5 ± 0.1（凯勒林A）和5.9 ± 0.9（凯勒林B）μM，而其他化合物的细胞毒性较小（IC > 20 μM）。
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