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

• 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: (4R,4aS,6aR,9S,11aR,11bS,E)-8-(hydroxyimino)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylic acid
• 英文别名: Isosteviol 16-oxime；Isosteviol oxime；(1R,4S,5R,9S,10R,13S,14E)-14-hydroxyimino-5,9,13-trimethyltetracyclo[11.2.1.01,10.04,9]hexadecane-5-carboxylic acid
• 化学式: C₂₀H₃₁NO₃
• 分子量: 333.471
• InChiKey: VAPPWLUSZRLUPV-AKWMADHGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  69.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R,4aS,6aR,9S,11aR,11bS,E)-8-(hydroxyimino)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylic acid 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82%的产率得到ent-16-aminobeyeran-19-oic acid
  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 吡啶 、 盐酸羟胺 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以100%的产率得到(4R,4aS,6aR,9S,11aR,11bS,E)-8-(hydroxyimino)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and In Vivo Acute Antihyperglycemic Evaluation of Novel Isosteviol Derivatives

  摘要：

  异雌二醇是一种具有多种生物活性的四环双萜类化合物。本文合成了一系列含有 C-18 羧基（5-12）、C-16羰基（14-16）和与异塞维醇结构融合的含杂原子框架（18-19）的新型异塞维醇衍生物，并对其体内急性抗高血糖作用进行了评估。其中，化合物 8 的抗高血糖作用最强。此外，还主要分析了结构-活性关系（SAR）。所有新合成化合物的结构都是通过 1H、13CNMR、MS、IR 和基本分析确定的。

  DOI：

  10.2174/157018010792929522

文献信息

• Synthesis and In Vivo Acute Antihyperglycemic Evaluation of Novel Isosteviol Derivatives
  作者：Junqing Chen、Xiaoming Zha、Min Sun、Jin Cai、Wen Zhou、Min Ji

  DOI：10.2174/157018010792929522

  日期：2010.11.1

  Isosteviol is a beyerane tetracyclic diterpenoid with a large variety of biological activities. In this article, a series of novel isosteviol derivatives containing the modification of C-18 carboxyl group (5-12), C-16 carbonyl group (14- 16) and heteroatom-containing frameworks fused with isosteviol structure (18-19) were synthesized and evaluated for their in vivo acute antihyperglycemeric effects. Among them, compound 8 exhibited the most potent antihyperglycemeric effects. Furthermore, primarily, structure-activity relationship (SAR) was also analyzed. The structures of all the newly synthesized compounds were determined by 1H, 13CNMR, MS, IR and elementary analysis.

  异雌二醇是一种具有多种生物活性的四环双萜类化合物。本文合成了一系列含有 C-18 羧基（5-12）、C-16羰基（14-16）和与异塞维醇结构融合的含杂原子框架（18-19）的新型异塞维醇衍生物，并对其体内急性抗高血糖作用进行了评估。其中，化合物 8 的抗高血糖作用最强。此外，还主要分析了结构-活性关系（SAR）。所有新合成化合物的结构都是通过 1H、13CNMR、MS、IR 和基本分析确定的。
• 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.
• Transformation of isosteviol oxime to a lactone under Beckmann reaction conditions
  作者：Olesya I. Militsina、Galina I. Kovyljaeva、Galina A. Bakaleynik、Irina Yu. Strobykina、Vladimir E. Kataev、Vladimir A. Alfonsov、Rashid Z. Musin、Dmitry V. Beskrovny、Igor A. Litvinov

  DOI：10.1070/mc2005v015n01abeh001946

  日期：2005.1

  Heating the 16-E-oxime of isosteviol (ent-16-E-hydroxyiminobeyeran-19-oic acid) with concentrated hydrochloric acid (or 25% H2SO4) at 110 degreesC leads to the formation of lactone of 4alpha-carboxy-13alpha-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid as the main product, whereas approximately equal quantities of this lactone and lactam of 4alpha-carboxy- 13alpha-amino- 13,16- seco-ent-19 norbeyeran-16-oic acid are formed by heating the 16-E-oxime of isosteviol with concentrated hydrochloric acid in an ampoule at 180 degreesC.
• Microbial transformation of isosteviol oxime and the inhibitory effects on NF-κB and AP-1 activation in LPS-stimulated macrophages☆
  作者：Shwu-Fen Chang、Bo-Hon Chou、Li-Ming Yang、Feng-Lin Hsu、Wen-Kuang Lin、Yi Ho、Shwu-Jiuan Lin

  DOI：10.1016/j.bmc.2009.07.029

  日期：2009.9.1

  Microbial transformation of isosteviol oxime (ent-16-E-hydroxyiminobeyeran-19-oic acid) (2) with Aspergillus niger BCRC 32720 and Absidia pseudocylindrospora ATCC 24169 yielded several compounds. In addition to bioconverting the D-ring to lactone and lactam moieties, 4 alpha-carboxy-13 alpha-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone (7) and 4 alpha-carboxy-13 alpha-amino-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactam (10), one known compound, ent-1 beta, 7 alpha-dihydroxy-16-oxo-beyeran-19-oic acid (6), and five new compounds, ent-7 alpha-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (3), ent-1 beta, 7 alpha-dihydroxy-16-E-hydroxyiminobeyeran-19-oic acid (4), ent-1 beta-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (5), ent-8 beta-cyanomethyl-13-methyl-12-podocarpen-19-oic acid (8), and ent-8 beta-cyanomethyl-13-methyl-13-podocarpen-19-oic acid (9), were isolated from the microbial transformation of 2. Elucidation of the structures of these isolated compounds was primarily based on 1D and 2D NMR, and HRESIMS data, and 3-5 were further confirmed by X-ray crystallographic analyses. Additionally, the inhibitory effects of all of these compounds were evaluated on NF-kappa B and AP-1 activation in LPS-stimulated RAW 264.7 macrophages. Among the compounds tested, 5 and 10 significantly inhibited NF-kappa B activation, with 5 showing equal potency to dexamethasone; 3 and 6-9 significantly inhibited AP-1 activation, particularly 8, which showed more inhibitory activity than dexamethasone. (C) 2009 Elsevier Ltd. 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.