3β-Hydroxyolean-9(11),12-dien-30-oic acid | 14884-88-9

• 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: 3β-Hydroxyolean-9(11),12-dien-30-oic acid
• 英文别名: 3β-hydroxyolean-9(11),12(13)-dien-30-oic acid；3β-hydroxy-18βH-olean-9(10),11(12)-dien-30-oic acid；9.11-Dehydro-11-deoxo-18β-glycyrrhetic acid；3β-hydroxy-18βH-olean-9(11),12(13)-dien-30-oic acid；(3β,18β,20β)-3-hydroxy-olean-9(11),12-dien-29-oic acid；(3β,18β,20β)-3-hydroxyoleana-9(11),12-dien-29-oic acid；3β-hydroxy-oleanadien-(9(11).12)-oic acid-(30)；3β-Hydroxy-oleanadien-(9(11).12)-saeure-(30)；9(11)-Dehydroglycyrrhetic acid；(2S,4aS,6aR,6bS,8aR,10S,12aS,14bR)-10-hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,7,8,8a,10,11,12,14b-dodecahydropicene-2-carboxylic acid
• CAS: 14884-88-9
• 化学式: C₃₀H₄₆O₃
• 分子量: 454.693
• InChiKey: DPWVNICGMWYCAP-KVIBWAOPSA-N

物化性质

• 沸点：
  566.1±50.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  33
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3β-Hydroxyolean-9(11),12-dien-30-oic acid 在 草酰氯 、 2-碘酰基苯甲酸 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 10.5h， 生成 (2S,4aS,6aR,6bS,8aR,12aR,14bR)-11-hydroxy-N,2,4a,6a,6b,9,9,12a-octamethyl-10-oxo-3,4,5,6,7,8,8a,14b-octahydro-1H-picene-2-carboxamide
  参考文献：
  名称：

  Discovery of a Potential Anti-Inflammatory Agent: 3-Oxo-29-noroleana-1,9(11),12-trien-2,20-dicarbonitrile

  摘要：

  Fifteen novel derivatives of glycyrrhetinic acid (GA) were synthesized and evaluated for anti-inflammatory activities. It was found that the introduction of 1-en-3-one and 9(11),12-diene and 2,20-dinitrile functionalities into the scaffold of GA led to the discovery of potent compound 19 for inhibition of LPS-induced NO production. Furthermore, 19 effectively inhibited the protein and mRNA expression of inducible NO synthase (iNOS) and the mRNA expression of TNF-alpha, IL-6, and IL-1 beta in LPS-stimulated RAW 264.7 macrophages. Mechanistically, 19 exerted inhibitory effects on the activation of the three main MAPKs and phosphorylation and degradation of I kappa B-alpha, as well as the ratio of nuclear/cytosolic content of p65. Importantly, 19 significantly decreased the mortality rate in the mouse model of LPS-induced sepsis shock. It is noteworthy that inhibitory effect of 19 on NO production was not blocked by the glucocorticoid receptor antagonist mifepristone, indicating that it does not act through the glucocorticoid receptor.

  DOI：

  10.1021/jm301652t
• 作为产物：
  描述：

  甘草次酸 在 钾硼氢 作用下， 以 乙醇 为溶剂， 生成 3β-Hydroxyolean-9(11),12-dien-30-oic acid
  参考文献：
  名称：

  甘草次酸和齐墩果酸的一些衍生物的制备。

  摘要：

  摘要：制备和表征了一些甘草酸和齐墩果酸的新衍生物。根据需要合成了修改和正常官能团的各种组合，以便对甘草酸和齐墩果酸的解耦活性进行单独研究。这两种酸的羟基功能被修改为β-羧丙酰基、乙酰基和β-甲氧羰基丙酰酯。甘草酸的羧基功能转化为酰胺、对-氨基苯甲酸、邻-氨基苯甲酸和该酸的甘氨酸结合物。制备了11-去氧（甘草酸）和9,11-脱氢-11-去氧（来自两种酸）的类似物。合成了齐墩果酸的11-酮类似物以及甲酯。

  DOI：

  10.1111/j.2042-7158.1967.tb08011.x

文献信息

• GAOH衍生物及其医药用途
  申请人：武汉华纳联合药业有限公司

  公开号：CN104530176B

  公开（公告）日：2016-03-23

  本发明提供一种全新结构的GAOH衍生物，该类化合物对炎症性肠病、肝炎病毒、足肿胀、耳肿胀、关节炎、肺炎、肾炎、鼻炎、脑卒中、心肌缺血、动脉粥样硬化、心律失常、自身免疫性疾病、老年痴呆、抑郁症、精神分裂症、恶性肿瘤及肿瘤辅助治疗、病毒感染性疾病、消化性溃疡、镇痛、抗过敏、抗内毒素、抗休克、糖尿病或糖尿病并发症具有很好的疗效。
• Effective Synthesis of 3β-Hydroxy-18βH-Olean-9(11),12 (13)-Dien-30-Oic Acid
  作者：V. A. Vydrina、A. A. Kravchenko、K. S. Denisova、M. P. Yakovleva、G. Yu. Ishmuratov

  DOI：10.1007/s10600-016-1833-y

  日期：2016.9

  Herein, we communicate results for the synthesis of 3 -hydroxy-18 H-olean-9(11),12(13)-dien-30-oic acid (1), which is widely used as a platform for synthesizing compounds with pharmacological activity (anti-inflammatory, antiviral, antitumor, antioxidant, etc.) [1–3]. Conjugated diene 1 was prepared earlier [1, 3–5] from glycyrrhetic acid (GLA) 2 in two steps in overall yield 66% by treating the substrate

  在此，我们交流了 3-hydroxy-18 H-olean-9(11​​),12(13)-dien-30-oic acid (1) 的合成结果，该酸被广泛用作合成具有药理作用的化合物的平台。活性（抗炎、抗病毒、抗肿瘤、抗氧化等）[1-3]。共轭二烯 1 早先 [1, 3-5] 从甘草次酸 (GLA) 2 分两步制备，总产率为 66%，方法是用碱处理底物，在 THF-H2O 中用 10-60 倍摩尔过量的 NaBH4，然后用碱处理11 和 11-羟基衍生物 3 的中间差向异构混合物 (5.5:1) 脱水，通过在 THF 中回流。盐酸。
• Synthesis and NMR Spectra of New C-Modified Glycyrrhetic Acid Derivatives
  作者：A. S. Budaev、L. R. Mikhailova、L. V. Spirikhin、L. A. Baltina

  DOI：10.1007/s10600-014-0937-5

  日期：2014.5

  New oxidative and skeletal transformations of olean-9(11),12(13)-dien-30-oic acid that were based on ozonolysis and UV irradiation produced the 9α,11α-epoxide and opened ring C.

  基于臭氧化和紫外照射的新型氧化和骨架转化反应，生成了9α,11α-环氧化物和开启的C环的剌果-9(11)，12(13)-二烯-30-酸。
• Synthesis of new derivatives of 3β-hydroxy18βH-olean-9,12-dien-30-oic acid
  作者：L. R. Mikhailova、M. V. Khudobko、L. A. Baltina、L. V. Spirikhin、R. M. Kondratenko、L. A. Baltina

  DOI：10.1007/s10600-009-9336-8

  日期：2009.5

  Ring A was transformed and new A-homo-4-aza- and 3-cyano-3,4-seco-olean-4-ene derivatives of 3β-hydroxy18βH-olean-9,12-dien-30-oic acid were synthesized.

  环A被转化，合成了新的A-同源-4-氮和3-氰-3,4-秒-鞘烯-4-烯衍生物，具体为3β-羟基18βH-鞘烯-9,12-二烯-30-酸。
• Synthesis of new glycyrrhetinic acid derived ring A azepanone, 29-urea and 29-hydroxamic acid derivatives as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors
  作者：Rawindra Gaware、Rupesh Khunt、Laszlo Czollner、Christian Stanetty、Thierry Da Cunha、Denise V. Kratschmar、Alex Odermatt、Paul Kosma、Ulrich Jordis、Dirk Claßen-Houben

  DOI：10.1016/j.bmc.2011.02.005

  日期：2011.3

  Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 1 and type 2. Whereas inhibition of 11 beta-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11 beta-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. Recently, we published a series of hydroxamic acid derivatives of glycyrrhetinic acid showing high selectivity for 11 beta-HSD2. The most potent and selective compound is active against human 11 beta-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11 beta-HSD1. Starting from the lead compounds glycyrrhetinic acid and the hydroxamic acid derivatives, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11 beta-HSD1 and 11 beta-HSD2 in cell lysates. Here we describe novel 29-urea- and 29-hydroxamic acid derivatives of glycyrrhetinic acid as well as derivatives with the Beckman rearrangement of the 3-oxime to a seven-membered ring, and the rearrangement of the C-ring from 11-keto-12-ene to 12-keto-9(11)-ene. The combination of modifications on different positions led to compounds comprising further improved selective inhibition of 11 beta-HSD2 in the lower nanomolar range with up to 3600-fold selectivity. (C) 2011 Elsevier Ltd. All rights reserved.