ent-1α-O-acetyl-6β-hydroxy-7,14-isopropylidene ketal-15-oxo-7,20-epoxy-16-kaurene | 331282-95-2

• 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: ent-1α-O-acetyl-6β-hydroxy-7,14-isopropylidene ketal-15-oxo-7,20-epoxy-16-kaurene
• 英文别名: [(1S,2S,5S,8R,9R,13R,14S,15R,19S)-14-hydroxy-11,11,16,16-tetramethyl-6-methylidene-7-oxo-10,12,21-trioxahexacyclo[11.6.2.01,15.02,8.05,9.08,13]henicosan-19-yl] acetate
• CAS: 331282-95-2
• 化学式: C₂₅H₃₄O₇
• 分子量: 446.541
• InChiKey: ZCWQHGVIQLBZKC-FTQSFJOTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  32
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ent-1α-O-acetyl-6β-hydroxy-7,14-isopropylidene ketal-15-oxo-7,20-epoxy-16-kaurene 在 盐酸 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成
  参考文献：
  名称：

  Structural modification of oridonin via DAST induced rearrangement

  摘要：

  建立了一种新颖简洁的合成方法，用于从奥利多宁制备6,20-环氧ent-考鲁烷二萜化合物。

  DOI：

  10.1039/c8ra05728a
• 作为产物：
  描述：

  冬凌草甲素 在 4-二甲氨基吡啶 、 对甲苯磺酸 、 三乙胺 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 5.0h， 生成 ent-1α-O-acetyl-6β-hydroxy-7,14-isopropylidene ketal-15-oxo-7,20-epoxy-16-kaurene
  参考文献：
  名称：

  Structural modification of oridonin via DAST induced rearrangement

  摘要：

  建立了一种新颖简洁的合成方法，用于从奥利多宁制备6,20-环氧ent-考鲁烷二萜化合物。

  DOI：

  10.1039/c8ra05728a

文献信息

• 1-OXO/ACYLATION-14-ACYLATED ORIDONIN DERIVATIVE, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
  申请人：HANGZHOU BENSHENG PHARMACEUTICAL CO., LTD.

  公开号：US20140364490A1

  公开（公告）日：2014-12-11

  The present invention relates to the fields of natural medicine and medicinal chemistry, and more particularly to a 1-oxo/acylated-14-acylated oridonin derivative of a general formula (I) or a pharmaceutically acceptable salt thereof, a method for preparing the compounds, a pharmaceutical composition comprising the compounds, and application thereof in preparation of antitumor drugs.

  本发明涉及自然药物和药物化学领域，更特别地涉及一种通用式(I)的1-氧代/酰化-14-酰化奥利多宁衍生物或其药用盐，一种制备该化合物的方法，包含该化合物的药物组合物，以及其在抗肿瘤药物制备中的应用。
• The conversion of oridonin to spirolactone-type or enmein-type diterpenoid: Synthesis and biological evaluation of ent-6,7-seco-oridonin derivatives as novel potential anticancer agents
  作者：Lei Wang、Dahong Li、Shengtao Xu、Hao Cai、Hequan Yao、Yihua Zhang、Jieyun Jiang、Jinyi Xu

  DOI：10.1016/j.ejmech.2012.03.024

  日期：2012.6

  commercial available natural product oridonin (1), a practical synthesis of ent-6,7-seco-oridonin derivatives (2, 3, 5, and 9) was accomplished and their biological activities were evaluated. The conversion of spirolactone-type diterpenoid to enmein-type was first completed. The results demonstrated that all synthesized ent-6,7-seco-oridonin derivatives could markedly inhibit the proliferation of cancer

  从市售的天然产物冬凌草甲素（起始1），的一个实际合成ENT -6,7-开环-oridonin衍生物（2，3，5，和9）中的溶液来实现和它们的生物活性进行了评价。首先完成了螺内酯型二萜类化合物向半球蛋白型的转化。结果表明，所合成ENT -6,7-开环-oridonin衍生物可显着抑制癌细胞的增殖。与紫杉醇相比，最具细胞毒性的化合物5在A549细胞中具有相似的效力，而在Bel-7402细胞中具有较低的细胞毒性。化合物5也比在小鼠母体化合物与冬凌草甲素MGC-803胃癌更有效体内。然后进一步设计合成了一系列新颖的5的14- O-衍生物，它们具有比5更好的活性，并且在体外具有与紫杉醇相似的活性。本研究还讨论了冬凌草甲素衍生物的结构-活性关系。
• Novel anticancer oridonin derivatives possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: Design, synthesis, biological evaluation and nitric oxide release studies
  作者：Shengtao Xu、Guangyu Wang、Yan Lin、Yanju Zhang、Lingling Pei、Hong Yao、Mei Hu、Yangyi Qiu、Zhangjian Huang、Yihua Zhang、Jinyi Xu

  DOI：10.1016/j.bmcl.2016.04.068

  日期：2016.6

  Oridonin (1) is a complex ent-kaurane diterpenoid with unique antitumor profile, which is isolated from Isodon rubescens. In order to develop novel derivatives of oridonin with improved potency, a series of nitric oxide (NO)-releasing oridonin derivatives were synthesized by coupling diazeniumdiolates with oridonin and its semisynthesized analogues. Their in vitro antiproliferative activity, nitric

  Oridonin（1）是一种具有独特抗肿瘤特性的复杂对映型月桂烷双萜类化合物，它是从红豆异形体中分离出来的。为了开发具有更高效能的冬凌草甲素的新型衍生物，通过将二醇二氮烯鎓盐与冬凌草甲素及其半合成类似物偶联，合成了一系列释放一氧化氮（NO）的冬凌草甲素。进一步评估了它们的体外抗增殖活性，一氧化氮释放能力和初步的抗癌机制。结果表明，所有目标化合物均表现出有效的抗增殖活性，IC50值为1.84至17.01μM。此外，观察到在大多数情况下，抗增殖活性与细胞内NO释放水平密切相关。更有趣的是，初步的机理研究表明，最有效的化合物14d诱导了Bel-7402细胞的凋亡，并使细胞周期停滞在S期，这与母体化合物oridonin不同。在一起，上述有希望的结果保证了作为潜在的抗肿瘤药物的冬凌草甲素/ NO杂化物的进一步发展。
• Novel nitric oxide-releasing spirolactone-type diterpenoid derivatives with in vitro synergistic anticancer activity as apoptosis inducer
  作者：Dahong Li、Tong Han、Kangtao Tian、Shuang Tang、Shengtao Xu、Xu Hu、Lei Wang、Zhanlin Li、Huiming Hua、Jinyi Xu

  DOI：10.1016/j.bmcl.2016.07.059

  日期：2016.9

  Herein, we reported the cytotoxicity, NO-releasing property, and apoptosis induced ability of two series of novel nitric oxide-releasing spirolactone-type diterpenoid derivatives (10a-f and 15a-f). All the title compounds were more potent than oridonin (7) and parent compound (9 or 14) against human tumor Bel-7402, K562, MGC-803 and CaEs-17 cells. SARs were concluded based on above data. Compound 15d exhibited the strongest antiproliferative activity with the IC50 of 0.86, 1.74, 1.16 and 3.75 mu M respectively, and could produce high level (above 25 mu M) of NO at the time point of 60 min. Further mechanism evaluation showed that 15d could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations in Bel-7402 cells via mitochondria-related pathways. It was expected that the remarkable biological profile of the synthetic NO-releasing spirolactone-type diterpenoid analogs make them possible as promising candidates for the development of anticancer agents. (C) 2016 Elsevier Ltd. All rights reserved.
• Novel Hybrids of Natural Oridonin-Bearing Nitrogen Mustards as Potential Anticancer Drug Candidates
  作者：Shengtao Xu、Lingling Pei、Chengqian Wang、Yun-Kai Zhang、Dahong Li、Hequan Yao、Xiaoming Wu、Zhe-Sheng Chen、Yijun Sun、Jinyi Xu

  DOI：10.1021/ml500141f

  日期：2014.7.10

  A series of novel hybrids from natural product oridonin and nitrogen mustards were designed and synthesized to obtain more efficacious and less toxic antitumor agents. The antiproliferative evaluation showed that most conjugates were more potent than their parent compounds oridonin and clinically used nitrogen mustards against four human cancer cell lines (K562, MCF-7, Bel-7402, and MGC-803). Furthermore, the representative compounds 16a-c exhibited antiproliferative activities against the multidrug resistant cell lines (SW620/AD300 and NCI-H460/MX20). It was shown that the most effective compound 16b possesses a strong inhibitory activity with an IC50 value 21-fold lower than that of oridonin in MCF-7 cells and also exhibits selective cytotoxicity toward the cancer cells. Intriguingly, compound 16b has been demonstrated to significantly induce apoptosis and affect cell cycle progression in human hepatoma Bel-7402 cells.