(4R,4aR,6aR,9S,11aS,11bR)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylic acid | 2319-76-8

• 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,4aR,6aR,9S,11aS,11bR)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylic acid
• 英文别名: Dihydroisohibasaeure；ent-beyeran-19-oic acid；Isostevic acid；(10S)-13-methyl-17-nor-phyllocladan-19-oic acid；(10S)-13-Methyl-17-nor-phyllocladan-19-saeure；Dihydroisostersaeure；Stachansaeure；Isoteosaeure
• CAS: 2319-76-8；7643-51-8；20108-01-4
• 化学式: C₂₀H₃₂O₂
• 分子量: 304.473
• InChiKey: VHAZSZJVOSGWCB-VQSWZGCSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.26
• 重原子数：
  22.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  37.3
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  (4R,4aR,6aR,9S,11aS,11bR)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylic acid 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以82%的产率得到ent-beyer-19-ol
  参考文献：
  名称：

  ent-Beyerane Diterpenes as a Key Platform for the Development of ArnT-Mediated Colistin Resistance Inhibitors

  摘要：

  Colistin is a last-resort antibiotic for the treatment of multidrug resistant Gram-negative bacterial infections. Recently, a natural ent-beyerene diterpene was identified as a promising inhibitor of the enzyme responsible for colistin resistance mediated by lipid A aminoarabinosylation in Gram-negative bacteria, namely, ArnT (undecaprenyl phosphate-alpha-4-amino-4-deoxy-L-arabinose arabinosyl transferase). Here, semisynthetic analogues of hit were designed, synthetized, and tested against colistin-resistant Pseudomonas aeruginosa strains including clinical isolates to exploit the versatility of the diterpene scaffold. Microbiological assays coupled with molecular modeling indicated that for a more efficient colistin adjuvant activity, likely resulting from inhibition of the ArnT activity by the selected compounds and therefore from their interaction with the catalytic site of ArnT, an ent-beyerane scaffold is required along with an oxalate-like group at C-18/C-19 or a sugar residue at C-19 to resemble L-Ara4N. The ent-beyerane skeleton is identified for the first time as a privileged scaffold for further cost-effective development of valuable colistin resistance inhibitors.

  DOI：

  10.1021/acs.joc.0c01459
• 作为产物：
  描述：

  ent-beyer-19-ol 在 chromium(VI) oxide 、 溶剂黄146 作用下， 生成 (4R,4aR,6aR,9S,11aS,11bR)-4,9,11b-trimethyltetradecahydro-6a,9-methanocyclohepta[a]naphthalene-4-carboxylic acid
  参考文献：
  名称：

  的成分Erythroxylon monogynum的罗。第I部分：（+）-Hibaene，[（+）-stachene]，赤藓醇A（一丁香酚），赤藓醇B和赤藓糖醇A

  摘要：

  根据它们的光谱性质和化学反应来确定（+）-hibaene（2），赤藓醇A（3），赤藓醇B（8）和赤藓醇A（11）的组成和立体化学。红血球二醇A已被转化为赤藓醇A，赤藓醇A和B均已被转化为（+）-hibaene。赤藓醇B中双键与伯醇功能的关系已通过氧化裂解确定。已经研究了赤藓醇A的硼氢化产物。

  DOI：

  10.1039/j39680002349

文献信息

• The biotransformation of some ent-beyeran-19-oic acids by Gibberella fujikuroi
  作者：Mohammad Shaiq Ali、James R. Hanson、Bras H. de Oliveira

  DOI：10.1016/0031-9422(92)90026-m

  日期：1992.2

  ent -beyeran-19-oic acid), ent -16β-hydroxybeyeran-19-oic acid, and ent -16β-hydroxy-16α-methylbeyeran-19-oic acid by Gibberella fujikuroi has been shown to give ring A desoxybeyergibberellin analogues of GA 9 , GA 12 and GA 25 . The ent -16β-hydroxybeyeran-19-oic acid also gave some hydroxylated beyeranes and the 7β-hydroxybeyeranolide.

  摘要 藤黑赤霉对异甜菊酸 (ent -beyeran-19-oic acid)、ent -16β-hydroxybeyeran-19-oic acid 和 ent -16β-hydroxy-16α-methylbeyeran-19-oic acid 的生物转化已被证明是得到 GA 9 、GA 12 和 GA 25 的环 A 脱氧拜耳赤霉素类似物。ent -16β-hydroxybeyeran-19-oic acid 也产生了一些羟基化的 beyeranes 和 7β-hydroxybeyeranolide。
• Anodic Decarboxylation of Isostevic Acid
  作者：James A. Waters、Edwin D. Becker、Erich Mosettig

  DOI：10.1021/jo01059a533

  日期：1962.12
• STEVIOSIDE. II. THE STRUCTURE OF THE AGLUCON
  作者：ERICH MOSETTIG、WILLIAM R. NES

  DOI：10.1021/jo01125a013

  日期：1955.7
• Oxygenated compounds from the bioconversion of isostevic acid and their inhibition of TNF-α and COX-2 expressions in LPS-stimulated RAW 264.7 cells
  作者：Li-Ming Yang、Shwu-Fen Chang、Wen-Kuang Lin、Bo-Hon Chou、Li-Hsuan Wang、Pan-Chun Liu、Shwu-Jiuan Lin

  DOI：10.1016/j.phytochem.2011.12.006

  日期：2012.3

  Fourteen oxygenated compounds were isolated from the preparative-scale biotransformation of isostevic acid (ent-beyeran-19-oic acid). Incubation of it with Aspergillus niger BCRC 32720 produced eight metabolites, four with Bacillus megaterium ATCC 14581, and another four with Mortierella isabellina ATCC 38063. In addition to their structural elucidation by NMR spectroscopy and HRMS, structures of four of these were further confirmed by X-ray diffraction studies. Real-time reverse transcription PCR analysis found that 15 of these compounds displayed significant in vitro anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 macrophages by reducing the levels of both TNF-alpha and COX-2 mRNA relative to control cells stimulated by LPS alone. The activity of one metabolite was similar to that of dexamethasone in inhibiting the expression of TNF-alpha mRNA, while all test compounds except two of them were more potent than dexamethasone in inhibiting the expression of the COX-2 mRNA. (C) 2011 Elsevier Ltd. All rights reserved.