dihydroagathic acid | 5956-15-0

• 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: dihydroagathic acid
• 英文别名: (1S,4aR,5S,8aR)-5-(4-carboxy-3-methylbutyl)-1,4a-dimethyl-6-methylidene-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carboxylic acid
• CAS: 5956-15-0
• 化学式: C₂₀H₃₂O₄
• 分子量: 336.472
• InChiKey: HPQKNJHVWUWAOR-OVODCCOESA-N

物化性质

• 沸点：
  486.7±38.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)
• LogP：
  5.003 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  dihydroagathic acid 在 氢溴酸 、 溶剂黄146 作用下， 反应 24.0h， 以86%的产率得到
  参考文献：
  名称：

  Synthesis and Pharmacological Activity of Diterpenylnaphthoquinone Derivatives

  摘要：

  从junicedric酸和lapachol制备了新的二萜基醌，它结合了二萜二酸和萘醌。通过小鼠HCl-EtOH诱导的胃损伤模型以及以下人类细胞系的基底细胞毒性，评估了这些新衍生物作为胃保护剂的作用：正常肺成纤维细胞（MRC-5）、胃上皮腺癌（AGS）和肝细胞癌（Hep G2）。其中几种新化合物作为抗溃疡剂具有显著活性，并显示出对AGS细胞的选择性细胞毒性。

  DOI：

  10.3390/molecules16108614
• 作为产物：
  描述：

  玛瑙酸 在 sodium 、 正丁醇 作用下， 生成 dihydroagathic acid
  参考文献：
  名称：

  Carman,R.M.; Craig,W.J., Australian Journal of Chemistry, 1971, vol. 24, p. 2379 - 2388

  摘要：

  DOI：

文献信息

• Synthesis, Gastroprotective Effect and Cytotoxicity of New Amino Acid Diterpene Monoamides and Diamides
  作者：Guillermo Schmeda-Hirschmann、Mariano Walter Pertino、Jaime A. Rodriguez、Francisco Monsalve、Daniel Droguett、Cristina Theoduloz

  DOI：10.3390/molecules15107378

  日期：——

  Following our studies on the gastroprotective effect and cytotoxicity of terpene derivatives, new amides were prepared from the diterpene 8(17)-labden-15,19-dioic acid (junicedric acid) and its 8(9)-en isomer with C-protected amino acids (amino acid esters). The new compounds were evaluated for their gastroprotective effect in the ethanol/HCl-induced gastric lesions model in mice, as well as for cytotoxicity using the following human cell lines: normal lung fibroblasts (MRC-5), gastric adenocarcinoma cells (AGS) and liver hepatocellular carcinoma (Hep G2). A dose-response experiment showed that at 25 mg/kg the C-15 leucyl and C-15,19-dileucylester amides of junicedric acid reduced gastric lesions by about 65.6 and 49.6%, respectively, with an effect comparable to lansoprazole at 20 mg/kg (79.3% lesion reduction). The comparison of the gastroprotective effect of 18 new amino acid ester amides was carried out at a single oral dose of 25 mg/kg. Several compounds presented a strong gastroprotective effect, reducing gastric lesions in the 70.9-87.8% range. The diprolyl derivative of junicedric acid, the most active product of this study (87.8% lesion reduction at 25 mg/kg) presented a cytotoxicity value comparable with that of the reference compound lansoprazole. The structure-activity relationships are discussed.

  在对萜烯衍生物的胃保护作用和细胞毒性进行研究之后，我们利用二萜 8(17)-labden-15,19-dioic acid（朱尼地酸）及其 8(9)-en 异构体与 C 保护氨基酸（氨基酸酯）制备了新的酰胺。在乙醇/HCl 诱导的小鼠胃损伤模型中，对这些新化合物的胃保护作用进行了评估，并使用以下人体细胞系对其细胞毒性进行了评估：正常肺成纤维细胞（MRC-5）、胃腺癌细胞（AGS）和肝脏肝细胞癌（Hep G2）。剂量反应实验显示，在 25 毫克/千克的剂量下，朱尼地酸的 C-15 白基和 C-15,19-二异丁基酰胺可分别减少约 65.6% 和 49.6% 的胃部病变，其效果与 20 毫克/千克的兰索拉唑相当（病变减少 79.3%）。在单次口服剂量为 25 毫克/千克时，对 18 种新的氨基酸酯酰胺的胃保护作用进行了比较。有几种化合物具有很强的胃保护作用，可使胃部病变减少 70.9%-87.8%。朱尼地酸的二甘醇衍生物是本研究中最活跃的产品（25 毫克/千克的剂量可减少 87.8% 的病变），其细胞毒性值与参考化合物兰索拉唑相当。本文讨论了结构-活性关系。
• In Vitro Biotransformations of Isocupressic Acid by Cow Rumen Preparations:  Formation of Agathic and Dihydroagathic Acids
  作者：Shwu-Jiuan Lin、Robert E. Short、Stephen P. Ford、Elaine E. Grings、John P. N. Rosazza

  DOI：10.1021/np970372u

  日期：1998.1.1

  Isocupressic acid [15-hydroxylabda-8(17),13E-dien-19-oic acid] (I) was incubated under anaerobic conditions for 48 h in an in vitro luminal fluid mixture and was transformed into two metabolites. The two metabolites were identified by GC/MS as agathic acid [labda-8(17),13(E)-diene-15,19-dioic acid] (4E) and dihydroagathic acid [labda-8(17)-ene-15,19-dioic acid] (6). Metabolite identities were confirmed by chemical conversions of isocupressic acid (1) and imbricataloic acid (5) into 4E and 6, respectively. Structures of synthetic metabolites were confirmed by H-1 and C-13 NMR, specific rotation, GC/MS, and high-resolution mass spectrometry. Plasma obtained from cows that were fed Ponderosa pine needles contained (13R,S)-dihydroagathic acid (6) but not isocupressic acid (1) or 4E. The results suggest that isocupressic acid (1) is metabolically oxidized to agathic acid (4E), subsequently reduced to (13R,S)-dihydroagathic acid (6) in the rumen, and then absorbed into the bloodstream of cattle.
• Preparation of Tetrahydroagathic Acid:  A Serum Metabolite of Isocupressic Acid, a Cattle Abortifacient in Ponderosa Pine
  作者：Massoud Garrossian、Dale R. Gardner、Kip E. Panter、Lynn F. James

  DOI：10.1021/jf011501m

  日期：2002.4.1

  Isocupressic acid (1) was used to synthetically prepare a mixture of (8S,13R,S)-labda-15,19-dioic acid (tetrahydroagathic acid) (5) via a two-step oxidation procedure followed by hydrogenation of the double bonds at C13 and C8. Reduction of the C8,17 double bond was stereospecific producing only the 8S isomer and confirmed by the nOe interaction between the resulting C17 and C20 methyl groups. The 13R and 13S isomers of 5 were separated and analyzed by HPLC/MS, and (13S)tetrahydroagathic acid was isolated and identified by comparison to a standard prepared by hydrogenation of naturally occurring (13S)-dihydroagathic acid (4). (13R,S)-dihydroagathic acid was prepared by selective sodium metal-catalyzed hydrogenation of the C13,14 allylic double bond of agathic acid (3). The prepared compounds were then used as standards to confirm the presence of 4 and 5 and their respective 13R and 13S isomers in bovine serum samples. Tetrahydroagathic acid was shown to be the only metabolite detected in serum samples taken from a suspected cattle abortion case submitted for diagnosis; and, thus, 5 could be a valuable diagnostic marker for pine needle-induced abortions.
• Carman,R.M.; Craig,W.J., Australian Journal of Chemistry, 1971, vol. 24, p. 2379 - 2388
  作者：Carman,R.M.、Craig,W.J.

  DOI：——

  日期：——
• Synthesis and Pharmacological Activity of Diterpenylnaphthoquinone Derivatives
  作者：Mariano Walter Pertino、Cristina Theoduloz、Jose Antonio Palenzuela、Maria del Mar Afonso、Erdem Yesilada、Francisco Monsalve、Paulo González、Daniel Droguett、Guillermo Schmeda-Hirschmann

  DOI：10.3390/molecules16108614

  日期：——

  New diterpenylquinones, combining a diterpene diacid and a naphthoquinone, were prepared from junicedric acid and lapachol. The new derivatives were assessed as gastroprotective agents by the HCl-EtOH-induced gastric lesions model in mice as well as for basal cytotoxicity on the following human cell lines: Normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), and hepatocellular carcinoma (Hep G2). Several of the new compounds were significantly active as antiulcer agents and showed selective cytotoxicity against AGS cells.

  从junicedric酸和lapachol制备了新的二萜基醌，它结合了二萜二酸和萘醌。通过小鼠HCl-EtOH诱导的胃损伤模型以及以下人类细胞系的基底细胞毒性，评估了这些新衍生物作为胃保护剂的作用：正常肺成纤维细胞（MRC-5）、胃上皮腺癌（AGS）和肝细胞癌（Hep G2）。其中几种新化合物作为抗溃疡剂具有显著活性，并显示出对AGS细胞的选择性细胞毒性。