3β,11-Dihydroxyolean-12-en-30-oic 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: 3β,11-Dihydroxyolean-12-en-30-oic acid
• 英文别名: (3β,18β,20β)-3,11-dihydroxyoleana-12-en-29-oic acid；11-hydroxylglycyrrhetinic acid；(3β,18β,20β)-3,11-dihydroxyolean-12-en-29-oic acid；(2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-10,13-dihydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-2-carboxylic acid
• 化学式: C₃₀H₄₈O₄
• 分子量: 472.709
• InChiKey: WTYUUMRZSINYLI-IQZSAIRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  34
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3β,11-Dihydroxyolean-12-en-30-oic acid 在 盐酸 、 草酰氯 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 26.5h， 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 sodium tetrahydroborate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 3β,11-Dihydroxyolean-12-en-30-oic acid
  参考文献：
  名称：

  3β-Hydroxy-18βH-Olean-9(11​​),12(13)-Dien-30-Oic Acid的有效合成

  摘要：

  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。

  DOI：

  10.1007/s10600-016-1833-y

文献信息

• Synthesis of methyl 2-cyano-3,12-dioxo-18β-olean-1,9(11)-dien-30-oate analogues to determine the active groups for inhibiting cell growth and inducing apoptosis in leukemia cells
  作者：Xiaojing Li、Yuetong Wang、Yuan Gao、Lei Li、Xin Guo、Dan Liu、Yongkui Jing、Linxiang Zhao

  DOI：10.1039/c4ob00703d

  日期：——

  Fourteen of the methyl 2-cyano-3,12-dioxo-18β-olean-1,9(11)-dien-30-oate (CDODO-Me-12, 10d) analogues with different structures of ring C were synthesized to determine the active groups for inhibiting cell growth and inducing apoptosis in human leukemia HL-60 cells. An unsaturated group in ring C was required to maintain the ability to inhibit cell growth and induce apoptosis. Compound 10e with 9(11),12-dien in ring C displayed comparable apoptosis induction ability to 10d associated with decreased levels of c-FLIP, but not Mcl-1 and XIAP. Compound 10e had decreased ability to deplete GSH compared to compound 10d. Compound 10e represents a new active compound acting through a different mechanism from that of compound 10d.

  合成了14种具有不同C环结构的2-氰基-3,12-二氧-18β-油烯-1,9(11)-二烯-30-酸甲酯(CDODO-Me-12，10d)类似物，以确定抑制人白血病HL-60细胞增殖和诱导凋亡的活性基团。C环中需要一个不饱和基团来维持抑制细胞增殖和诱导凋亡的能力。C环中具有9(11),12-二烯的化合物10e显示出了与10d相当的诱导凋亡能力，这与其降低了c-FLIP而非Mcl-1和XIAP的水平有关。与化合物10d相比，化合物10e的耗竭谷胱甘肽能力降低。化合物10e是一种通过不同于化合物10d的作用机制发挥活性的新型活性化合物。
• 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 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.