4,8-二羟基-3,6,9-三亚甲基-3a,4,5,6a,7,8,9a,9b-八氢薁并[5,4-d]呋喃-2-酮 | 31565-50-1

• 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
• 中文名称: 4,8-二羟基-3,6,9-三亚甲基-3a,4,5,6a,7,8,9a,9b-八氢薁并[5,4-d]呋喃-2-酮
• 英文名称: deacylcynaropicrin
• 英文别名: desacylcynaropicrin；(1R,3S,5R,6R,7R,8S)-3-hydroxy-13,14,15-trimethylene-12-oxododecahydroazuleno[6,7-β]furan-8-yl methacrylate；(3aR,4S,6aR,8S,9aR,9bR)-4,8-dihydroxy-3,6,9-trimethylidene-3a,4,5,6a,7,8,9a,9b-octahydroazuleno[4,5-b]furan-2-one
• CAS: 31565-50-1
• 化学式: C₁₅H₁₈O₄
• 分子量: 262.306
• InChiKey: VPRPYNVJJXOFKZ-SNIKSBKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,8-二羟基-3,6,9-三亚甲基-3a,4,5,6a,7,8,9a,9b-八氢薁并[5,4-d]呋喃-2-酮 在 吡啶 、 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 12.17h， 生成 diacetoxyisolippidiol
  参考文献：
  名称：

  来自 Tricholepis glaberrima 的愈创木内酯

  摘要：

  摘要 环苦苦苷和11,13-二氢脱酰基苦苦苷是从毛毛虫中分离得到的。

  DOI：

  10.1016/s0031-9422(00)95292-0
• 作为产物：
  描述：

  (1R,3S,5R,6R,7R,8S)-3-(methoxymethoxy)-13,14,15-trimethylene-12-oxododecahydroazuleno[6,7-β]furan-4-yl 17-((methoxymethoxy)methyl)acrylate 在 水 、 4-甲基苯磺酸吡啶 、 sodium hydroxide 作用下， 以 叔丁醇 为溶剂， 反应 56.0h， 生成 4,8-二羟基-3,6,9-三亚甲基-3a,4,5,6a,7,8,9a,9b-八氢薁并[5,4-d]呋喃-2-酮
  参考文献：
  名称：

  Antitrypanosomal structure–activity-relationship study of synthetic cynaropicrin derivatives

  摘要：

  Cynaropicrin is a guaianolide sesquiterpene lactone with a 5-7-5 tricyclic skeleton, four exo-olefins, and two hydroxyl groups. Recently, it was found that the compound is a potent in vitro and in vivo inhibitor of the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT; sleeping sickness). In this Letter, chemical derivatization of cynaropicrin and the structure-activity-relationship (SAR) study against T. brucei is described. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.099

文献信息

• Structure-Activity Relationship Study of Sesquiterpene Lactones and Their Semi-Synthetic Amino Derivatives as Potential Antitrypanosomal Products
  作者：Stefanie Zimmermann、Gerda Fouché、Maria De Mieri、Yukiko Yoshimoto、Toyonobu Usuki、Rudzani Nthambeleni、Christopher Parkinson、Christiaan van der Westhuyzen、Marcel Kaiser、Matthias Hamburger、Michael Adams

  DOI：10.3390/molecules19033523

  日期：——

  Sesquiterpene lactones (STLs) are natural products that have potent antitrypanosomal activity in vitro and, in the case of cynaropicrin, also reduce parasitemia in the murine model of trypanosomiasis. To explore their structure-antitrypanosomal activity relationships, a set of 34 natural and semi-synthetic STLs and amino-STLs was tested in vitro against T. b. rhodesiense (which causes East African sleeping sickness) and mammalian cancer cells (rat bone myoblast L6 cells). It was found that the α-methylene-γ-lactone moiety is necessary for both antitrypanosomal effects and cytotoxicity. Antitrypanosomal selectivity is facilitated by 2-(hydroxymethyl)acrylate or 3,4-dihydroxy-2-methylenebutylate side chains, and by the presence of cyclopentenone rings. Semi-synthetic STL amines with morpholino and dimethylamino groups showed improved in vitro activity over the native STLs. The dimethylamino derivative of cynaropicrin was prepared and tested orally in the T. b. rhodesiense acute mouse model, where it showed reduced toxicity over cynaropicrin, but also lost antitrypanosomal activity.

  倍半萜内酯（STL）是一种天然产品，在体外具有强大的抗锥虫活性，在犬鞭毛虫素的情况下，还能降低锥虫病小鼠模型中的寄生虫血症。为了探索它们的结构与抗锥虫活性之间的关系，我们对 34 种天然和半合成的 STL 和氨基 STL 进行了体外测试，以检测它们对罗得西亚锥虫（导致东非昏睡病）和哺乳动物癌细胞（大鼠骨肌母细胞 L6 细胞）的抗锥虫活性。结果发现，α-亚甲基-γ-内酯分子对于抗盘虫作用和细胞毒性都是必需的。2-（羟甲基）丙烯酸酯或 3,4-二羟基-2-亚甲基丁酸侧链以及环戊烯酮环的存在有助于提高抗盘虫选择性。与原生 STL 相比，带有吗啉基和二甲基氨基基团的半合成 STL 氨基化合物显示出更强的体外活性。我们制备了卡诺匹克林的二甲基氨基衍生物，并在罗得西亚锥虫病急性小鼠模型中进行了口服测试，结果表明该衍生物的毒性比卡诺匹克林低，但也失去了抗锥虫活性。
• 11,16 Oxetane lactones. Spectroscopic evidences and conformational analysis
  作者：Francisco A. Macías、Victor M.I. Viñolo、Frank R. Fronczek、Guillermo M. Massanet、José M.G. Molinillo

  DOI：10.1016/j.tet.2006.05.058

  日期：2006.8

  13-oxetane lactones, addition of a second Michael acceptor and reduction of the α-methylene-γ-lactone in order to future structure–activity relationship (SAR) studies. We have obtained all oxetane lactones stereoisomers at C-11 and C-16 positions. This fact has allowed us to establish some correlations between experimental data, derived by NMR and X-ray analysis, and the configuration at C-11 and C-16

  倍半萜内酯构成具有多种生物活性，包括化感作用的多种化合物。天然倍半萜内酯脱氢肋骨内酯和氰基吡啶青霉素已通过三种不同的方式进行了修饰：制备11,13-氧杂环丁烷内酯，添加第二个迈克尔受体和还原α-亚甲基-γ-内酯，以建立未来的结构-活性关系（SAR）研究。我们已经在C-11和C-16位置获得了所有的氧杂环丁烷内酯立体异构体。这一事实使我们能够建立由NMR和X射线分析得出的实验数据与C-11和C-16构型之间的一些相关性，这可能是建立立体化学以及确认化学结构的有用工具。在类似化合物上存在氧杂环丁烷环。
• Cynaropicrin and inhibition of NF-κB activation: A structure activity relationship study
  作者：Jing Li、Yusuke Yoshida、Manami Kurita、Toyonobu Usuki

  DOI：10.1016/j.bmcl.2019.04.004

  日期：2019.6

  photoaging of the skin by inhibiting the transcription activity of nuclear factor-kappa B (NF-κB). In this paper, nine chemical derivatives of cynaropicrin were prepared, and the structure activity relationship (SAR) study for NF-κB inhibition by measuring relative light units (RLU) was conducted.

  Cynaropicrin是一种具有5-7-5三环骨架，四个外烯烃和两个羟基的愈创木酚倍半萜内酯。该天然产物具有多种生物活性，包括抗炎特性和抗胰锥activity体活性。还发现通过抑制核因子-κB（NF-κB）的转录活性来抑制皮肤的光老化。本文制备了九种炔诺吡啶的化学衍生物，并通过测量相对光单位（RLU）进行了NF-κB抑制的结构活性关系（SAR）研究。
• Antiproliferative Activities of Cynaropicrin and Related Compounds against Cancer Stem Cells
  作者：Kousuke Araki、Minami Hara、Shohei Hamada、Takahiro Matsumoto、Seikou Nakamura

  DOI：10.1248/cpb.c23-00811

  日期：2024.2.20

  clinical practice. Therefore, the development of antiproliferative agents against CSCs is urgently required. In this study, we evaluated the antiproliferative activities of 21 sesquiterpenoids against human GBM U-251 MG CSCs and U-251 MG non-CSCs. Particularly, the guaianolide sesquiterpene lactone cynaropicrin (1) showed strong antiproliferative activity against U-251 MG CSCs (IC50 = 20.4 µM) and U-251

  尽管有多种癌症治疗方案可供选择，但胶质母细胞瘤 (GBM) 的死亡率仍然很高。尽管癌症干细胞（CSC）与不良预后和转移有关，并且在对现有抗癌药物和放射的抵抗中发挥着重要作用；目前尚无针对 CSC 的药物获批进入临床实践。因此，迫切需要开发针对CSC的抗增殖药物。在这项研究中，我们评估了 21 种倍半萜类化合物对人 GBM U-251 MG CSC 和 U-251 MG 非 CSC 的抗增殖活性。特别地，愈创木酚内酯倍半萜内酯洋蓟苦素( 1 )对U-251MG CSC(IC 50 = 20.4μM)和U-251MG非CSC(IC 50 = 10.9μM)表现出强抗增殖活性。因此，我们合成了1的六种衍生物并研究了它们的构效关系。大多数具有 α-亚甲基-γ-丁内酯部分的愈创木酚内酯倍半萜内酯对 U-251 MG 细胞表现出抗增殖活性。我们得出的结论是，5,7,5-环和 α-亚甲基-γ-丁内酯部分对于
• Guaiane Sesquiterpene Lactones and Amino Acid-Sesquiterpene Lactone Conjugates from the Aerial Parts of <i>Saussurea pulchella</i>
  作者：Min Cheol Yang、Sang Un Choi、Wahn Soo Choi、Sun Yeou Kim、Kang Ro Lee

  DOI：10.1021/np800005r

  日期：2008.4.1

  Two new guaiane sesquiterpene lactones (1 and 2) and seven new amino acid-sesquiterpene lactone conjugates (3-9), together with six known sesquiterpene lactones (10-15), were isolated from the methanol extract of the aerial parts of Saussurea pulchella. Their structures were determined on the basis of spectroscopic and chemical methods to be 8 alpha-O-(3'-hydroxy-3'-methylbutyryl)desacylcynaropicrin (1), 8 alpha-O-(2', 3'-dihydroxyisobutyryl)11 beta,13-dihydrodesacylcynaropicrin (2), and pulchellamines A, B, C, D, E, F, and G (3-9). The structures of the new amino acid-sesquiterpene lactone conjugates, pulchellamines A, B, C, D, E, F, and G (3-9), were confirmed by synthesis. The isolated compounds were evaluated for cytotoxic activity against four human tumor cell lines. Compounds 11 and 12 exhibited cytotoxicity against skin melanoma (SK-MEL-2) and ovary malignant ascites (SK-OV-3) human tumor cell lines with ED(50) values of 1.53 and 4.07 mu M, and 2.49 and 7.42 mu M, respectively.