ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-8-(hydroxyimino)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylate

• 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: ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-8-(hydroxyimino)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylate
• 英文别名: ethyl (1R,4S,5R,9S,10R,13S,14E)-14-hydroxyimino-5,9,13-trimethyltetracyclo[11.2.1.01,10.04,9]hexadecane-5-carboxylate
• 化学式: C₂₂H₃₅NO₃
• 分子量: 361.525
• InChiKey: OMALUWGOWZYSCJ-PSAYVOGOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  58.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-8-(hydroxyimino)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylate 在 氢气 、 镍 作用下， 以 四氢呋喃 为溶剂， 40.0 ℃ 、303.99 kPa 条件下， 反应 4.0h， 以88%的产率得到16-aminoisosteviol ethyl ester
  参考文献：
  名称：

  Stereoselective synthesis of bioactive isosteviol derivatives as α-glucosidase inhibitors

  摘要：

  Considerable interest has been attracted in isosteviol and its derivatives because of their large variety of pharmacological activities. In this project, a series of novel compounds containing hydroxyl, hydroxymethyl group and heteroatom-containing frameworks fused with isosteviol structure were synthesized and evaluated as alpha-glucosidase inhibitors, aimed at clarifying the structure-activity correlation. The results indicated that these isosteviol derivatives were capable of inhibiting in vitro alpha-glucosidase with moderate to good activities. Among them, indole derivative 15b exhibited the highest activities and thus may be exploitable as a lead compound for the development of potent alpha-glucosidase inhibitors. (c) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.01.017
• 作为产物：
  描述：

  异甜菊醇 在 盐酸羟胺 、 碳酸氢钠 、 potassium hydroxide 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 5.0h， 生成 ethyl (4R,4aS,6aR,9S,11aR,11bS,E)-8-(hydroxyimino)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylate
  参考文献：
  名称：

  作为蛋白酪氨酸磷酸酶-1B 抑制剂的异甜菊醇衍生物的合成、生物学评价和分子对接

  摘要：

  蛋白酪氨酸磷酸酶 (PTP1B) 拮抗胰岛素信号传导，并作为与肥胖和 II 型糖尿病相关的胰岛素抵抗的潜在治疗靶点。在这项工作中，合成了一系列异甜菊醇衍生物1-28 ，并通过体外双抗体夹心 ELISA (DAS-ELISA) 评估了对 PTP1B 的抑制活性。大多数异甜菊醇衍生物显示出中等的 PTP1B 抑制活性。其中，衍生物10、13、24、27具有显着的生物活性， IC 50值在0.24-0.40 μM之间。特别地，衍生物24对 PTP1B 表现出最好的抑制活性（IC50  = 0.24 µM)体外; 此外，它对 PTP1B 的选择性比T细胞蛋白酪氨酸磷酸酶 (TCPTP)高 7 倍，对 PTP1B 的选择性比细胞分裂周期 25 同系物 B (CDC25B) 高 14 倍。分子对接研究表明 PTP1B 中24和 LYS-116 残基之间的氢键相互作用可能对抑制活性至关重要。结果表明，衍

  DOI：

  10.1016/j.bmc.2023.117240

文献信息

• Discovery of novel, potent, isosteviol-based antithrombotic agents
  作者：Peng Chen、Dianwen Zhang、Meng Li、Qiong Wu、Yuko P.Y. Lam、Yan Guo、Chen Chen、Nan Bai、Shipra Malhotra、Wei Li、Peter B. O'Connor、Hongzheng Fu

  DOI：10.1016/j.ejmech.2019.111722

  日期：2019.12

  Thrombosis is a pathological coagulation process and can lead to many serious thrombotic diseases. Here, we report a novel potent antithrombotic compound (6k) based on isosteviol with anticoagulant and antiplatelet activities. 6k selectively inhibited FXa (K-i = 0.015 mu M) against a panel of serine proteases and showed excellent anticoagulant activity (significant prolongation of ex vivo PT and aPTT over the vehicle, p < 0.01). 6k also significantly inhibited ADP-induced platelet aggregation in rats relative to the vehicle (p < 0.01). Furthermore, 6k exhibited potent ex vivo and in vivo antithrombotic activity in rats relative to the vehicle (p < 0.01 and p < 0.0001, respectively). Novel structure 6k, with potent antithrombotic activity, is expected to lead a promising approach for the development of antithrombotic agents. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Stereoselective synthesis of bioactive isosteviol derivatives as α-glucosidase inhibitors
  作者：Ya Wu、Jing-Hua Yang、Gui-Fu Dai、Cong-Jun Liu、Guo-Qiang Tian、Wen-Yan Ma、Jing-Chao Tao

  DOI：10.1016/j.bmc.2009.01.017

  日期：2009.2

  Considerable interest has been attracted in isosteviol and its derivatives because of their large variety of pharmacological activities. In this project, a series of novel compounds containing hydroxyl, hydroxymethyl group and heteroatom-containing frameworks fused with isosteviol structure were synthesized and evaluated as alpha-glucosidase inhibitors, aimed at clarifying the structure-activity correlation. The results indicated that these isosteviol derivatives were capable of inhibiting in vitro alpha-glucosidase with moderate to good activities. Among them, indole derivative 15b exhibited the highest activities and thus may be exploitable as a lead compound for the development of potent alpha-glucosidase inhibitors. (c) 2009 Published by Elsevier Ltd.
• Isosteviol derivatives as protein tyrosine Phosphatase-1B inhibitors: Synthesis, biological evaluation and molecular docking
  作者：Na Li、Xinyu Li、Meidi Deng、Feifei Zhu、Zian Wang、Ruilong Sheng、Wenhui Wu、Ruihua Guo

  DOI：10.1016/j.bmc.2023.117240

  日期：2023.4

  a series of isosteviol derivatives 1–28 was synthesized and the inhibitory activity on PTP1B was evaluated by double antibody sandwich ELISA (DAS-ELISA) in vitro. Most isosteviol derivatives showed moderate PTP1B inhibitory activities. Among them, derivatives 10, 13, 24, 27 showed remarkable bioactivities with IC50 values ranging from 0.24 to 0.40 µM. Particularly, derivative 24 exhibited the best inhibitory

  蛋白酪氨酸磷酸酶 (PTP1B) 拮抗胰岛素信号传导，并作为与肥胖和 II 型糖尿病相关的胰岛素抵抗的潜在治疗靶点。在这项工作中，合成了一系列异甜菊醇衍生物1-28 ，并通过体外双抗体夹心 ELISA (DAS-ELISA) 评估了对 PTP1B 的抑制活性。大多数异甜菊醇衍生物显示出中等的 PTP1B 抑制活性。其中，衍生物10、13、24、27具有显着的生物活性， IC 50值在0.24-0.40 μM之间。特别地，衍生物24对 PTP1B 表现出最好的抑制活性（IC50  = 0.24 µM)体外; 此外，它对 PTP1B 的选择性比T细胞蛋白酪氨酸磷酸酶 (TCPTP)高 7 倍，对 PTP1B 的选择性比细胞分裂周期 25 同系物 B (CDC25B) 高 14 倍。分子对接研究表明 PTP1B 中24和 LYS-116 残基之间的氢键相互作用可能对抑制活性至关重要。结果表明，衍