ludartin

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ludartin
• 英文别名: (1S,2S,6S,12R,14S)-9,14-dimethyl-5-methylidene-3,13-dioxatetracyclo[8.4.0.02,6.012,14]tetradec-9-en-4-one
• 化学式: C₁₅H₁₈O₃
• 分子量: 246.306
• InChiKey: QXJYIGSXUBOSID-JZEMPJKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ludartin 在 copper(ll) sulfate pentahydrate 、 L-sodium ascorbate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 水 、 乙腈 、 叔丁醇 为溶剂， 反应 12.0h， 生成 (1S,2S,5R,6S,12R,14S)-9,14-dimethyl-5-[[[1-(4-nitrophenyl)triazol-4-yl]methylamino]methyl]-3,13-dioxatetracyclo[8.4.0.02,6.012,14]tetradec-9-en-4-one
  参考文献：
  名称：

  Click chemistry inspired facile synthesis and bioevaluation of novel triazolyl analogs of Ludartin

  摘要：

  A convenient and modular synthesis involving diastereoselective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction was carried out to furnish 1,4-disubstituted-1,2,3-triazoles of Ludartin. This reaction scheme involving Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction leading to the formation of triazolyl analogs is being reported for the first time. All the triazolyl products were characterised using spectral data analysis. Sulphorhodamine B cytotoxicity screening of the resulting products against a panel of five human cancerous cell-lines revealed that few of the analogs display promising broad spectrum cytotoxic effect. Among all the synthesized compounds, only 3q displayed the best cytotoxic effect with IC50 values of 12, 11, 38, 39 and 8.5 mu M but less than the standard Ludartin (1) with IC50 values of 6.3, 7.4, 7.5, 6.9 and 0.5 mu M against human neuroblastoma (T98G), lung (A-549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cell lines, respectively. The present synthesis was designed based on the previous literature reports of Ludartin as an aromatase inhibitor. Our work provides an initial study on structure-activity relationship of triazolyl analogs of sesquiterpene lactones in general and Ludartin (1) in particular. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.018

文献信息

• Synthetic Transformations of Sesquiterpene Lactones 10*. Synthesis of 13-Arylguaianolides
  作者：Anarkul S. Kihkentayeva、Elvira E. Shults、Yurii V. Gatilov、Sergey S. Patrushev、Sultan Karim、Gayane A. Atazhanova、Sergazy M. Adekenov

  DOI：10.1007/s10593-016-1967-7

  日期：2016.10

  The Heck reaction of methylidene lactones of guaiane type, arglabin and ludartin, with aryl halides occurs with the formation of the respective (E)- and (Z)-13-arylidene-substituted derivatives and the respective endocyclic isomer, the ratio of which depends on the nature of methylidenelactone and the reaction conditions. The arylation of ludartin occurred with a lower yield of the target products

  愈创甘油醚型亚甲基内酯，精氨酸和卢达汀与芳基卤化物的Heck反应与相应的（E）-和（Z）-13-亚芳基取代的衍生物以及相应的环内异构体的形成有关，其比例取决于甲基亚内酯的性质和反应条件 卢达汀的芳基化发生时目标产物的收率较低，并伴有马甲磺胺的形成。罗克海明与芳基卤化物在Heck反应下的相互作用导致环外产物具有（E）-和（Z）-构型，后者是主要的异构体。通过X射线结构分析确定了两种化合物的结构。
• Biomimetic Synthesis of Lavandiolides H, I, and K and Artematrolide F via Diels–Alder Reaction
  作者：Tian-Ze Li、Xiao-Tong Yang、Jin-Ping Wang、Chang-An Geng、Yun-Bao Ma、Li-Hua Su、Xue-Mei Zhang、Ji-Jun Chen

  DOI：10.1021/acs.orglett.1c03120

  日期：2021.11.5

  The biomimetic synthesis of guaianolide dimers lavandiolides H, I, and K and artematrolide F containing a spirolactone moiety has been accomplished for the first time from naturally abundant arglabin in four to six steps with an overall yield up to 60%, and a series of natural product-like guaianolide dimers, trimer, and tetramer were also successfully synthesized. Notably, the trimeric compound exhibited

  首次从天然丰富的阿甘油四到六步完成了愈创木酚内酯二聚体lavandiolides H、I和K和含有螺内酯部分的蒿内酯F的仿生合成，总收率高达60%，以及一系列天然还成功合成了类产品愈创木酚内酯二聚体、三聚体和四聚体。值得注意的是，三聚体化合物表现出比索拉非尼更有效的抗肝癌细胞毒性，IC 50值为 6.2 μM (HepG2)、6.8 μM (Huh7) 和 7.2 μM (SK-HEP-1)。
• Synthesis of new derivatives of natural guaianolides
  作者：S. M. Adekenov

  DOI：10.1007/s10600-013-0446-y

  日期：2013.1

  New derivatives with hydroxyl, amino, and keto groups; halides; and N atoms were synthesized based on available guaiane-type sesquiterpene lactones arglabin, artefin, ludartin, and estafiatin isolated from yarrow and wormwood. The structures of the molecules were established using IR, UV, PMR, and 13C NMR spectral data. The molecular structures of 2, 6, 12, and 14 were proved by x-ray crystal structure analyses.

  根据从西洋蓍草和艾草中分离出来的现有愈创木型倍半萜内酯 arglabin、artefin、ludartin 和 estafiatin，合成了带有羟基、氨基和酮基以及卤化物和 N 原子的新衍生物。利用红外光谱、紫外光谱、PMR 光谱和 13C NMR 光谱数据确定了这些分子的结构。通过 X 射线晶体结构分析，证明了 2、6、12 和 14 的分子结构。
• Synthesis and molecular structure of halohydrins of the guaianolide ludartin
  作者：R. I. Dzhalmakhanbetova、Yu V. Gatilov、M. M. Shakirov、G. A. Atazhanova、S. M. Adekenov

  DOI：10.1007/s10600-010-9574-9

  日期：2010.5

  Chloro—and bromhydrin derivatives of the sesquiterpene lactone ludartin were synthesized for the first time. Their structures were established by spectral data and an x-ray structure analysis.

  首次合成了倍半萜内酯络达汀的氯醇和溴醇衍生物。通过光谱数据和 X 射线结构分析确定了它们的结构。
• 10-Epideoxycumambrin b and other constituents of Stevia yaconensis var. subeglandulosa
  作者：Virginia E. Sosa、Juan C. Oberti、Roberto R. Gil、Edmundo A. Rúveda、Virgil L. Goedken、Alicia B、Gutiérrez、Werner Herz

  DOI：10.1016/s0031-9422(00)97888-9

  日期：1989.1

  Stevia yaconensis var. subeglandulosa afforded in addition to the known guaianolides ludartin and dehydroleucodin a new guaianolide 10-epi-8-deoxycumambrin B whose relative and absolute configurations were established by X-ray crystallography. Chemical transformations of ludartin established its relative and absolute stereochemistry.

  摘要 Stevia yaconensis var. 的地上部分。除了已知的愈创木酚内酯 ludartin 和脱氢亮氨酸之外，subeglandulosa 还提供了一种新的愈创木酚内酯 10-epi-8-deoxycumambrin B，其相对和绝对构型由 X 射线晶体学确定。ludartin 的化学转化建立了其相对和绝对立体化学。