(3β,20β)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-β-D-glucopyranuronosyl-β-D-glucopyranosiduronic acid 6′ ,6′’-dimethyl ester | 114006-81-4

• 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,20β)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-β-D-glucopyranuronosyl-β-D-glucopyranosiduronic acid 6′ ,6′’-dimethyl ester
• 英文别名: Glycyrrhizin-6 inverted exclamation marka,6 inverted exclamation marka inverted exclamation marka-dimethylester；(2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-10-[(2R,3R,4S,5S,6S)-4,5-dihydroxy-6-methoxycarbonyl-3-[(2R,3R,4S,5S,6S)-3,4,5-trihydroxy-6-methoxycarbonyloxan-2-yl]oxyoxan-2-yl]oxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid
• CAS: 114006-81-4；118525-41-0
• 化学式: C₄₄H₆₆O₁₆
• 分子量: 850.998
• InChiKey: VIBICZSYZZPALI-WGRDPETLSA-N

物化性质

• 沸点：
  900.1±65.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  60
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  245
• 氢给体数：
  6
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  (3β,20β)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-β-D-glucopyranuronosyl-β-D-glucopyranosiduronic acid 6′ ,6′’-dimethyl ester 在 sodium tetrahydroborate 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 9.0h， 生成
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Molecular Modeling of Glycyrrhizin Derivatives as Potent High-Mobility Group Box-1 Inhibitors with Anti-Heart-Failure Activity in Vivo

  摘要：

  Novel glycyrrhizin (GL) derivatives were designed and synthesized by introducing various amine or amino acid residues into the carbohydrate chain and at C-30. Their inhibitory effects on high-mobility group box 1 (HMGB1) were evaluated using a cell-based lipopolysaccharide (LPS) induced tumor necrosis factor alpha (TNF-alpha) release study. Compounds 10, 12, 18-20, 23, and 24, which had substituents introduced at C-30, demonstrated moderate HMGB1 inhibition with ED50 values ranging from 337 to 141 mu M, which are values comparable to that of the leading GL compound (1) (ED50 = 70 mu M). Compounds 23 and 24 emerged as novel and interesting HMGB1 inhibitors. These compounds were able to extend the survival of mice with chronic heart failure (CHF) and acute heart failure (AHF), respectively. In addition, molecular modeling studies were performed to support the biological data.

  DOI：

  10.1021/jm301248y
• 作为产物：
  描述：

  (3beta,20beta)-20-羧基-11-氧代-30-去甲齐墩果-12-烯-3-基 2-O-beta-D-吡喃葡糖基-beta-D-吡喃葡糖苷酸 在 盐酸 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以90%的产率得到(3β,20β)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-β-D-glucopyranuronosyl-β-D-glucopyranosiduronic acid 6′ ,6′’-dimethyl ester
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Molecular Modeling of Glycyrrhizin Derivatives as Potent High-Mobility Group Box-1 Inhibitors with Anti-Heart-Failure Activity in Vivo

  摘要：

  Novel glycyrrhizin (GL) derivatives were designed and synthesized by introducing various amine or amino acid residues into the carbohydrate chain and at C-30. Their inhibitory effects on high-mobility group box 1 (HMGB1) were evaluated using a cell-based lipopolysaccharide (LPS) induced tumor necrosis factor alpha (TNF-alpha) release study. Compounds 10, 12, 18-20, 23, and 24, which had substituents introduced at C-30, demonstrated moderate HMGB1 inhibition with ED50 values ranging from 337 to 141 mu M, which are values comparable to that of the leading GL compound (1) (ED50 = 70 mu M). Compounds 23 and 24 emerged as novel and interesting HMGB1 inhibitors. These compounds were able to extend the survival of mice with chronic heart failure (CHF) and acute heart failure (AHF), respectively. In addition, molecular modeling studies were performed to support the biological data.

  DOI：

  10.1021/jm301248y

文献信息

• Saponin and Sapogenol. XLVII. On the Constituents of the Roots of Glycyrrhiza uralensis Fischer from Northeastern China. 1. Licorice-Saponins A3, B2, and C2.
  作者：Isao KITAGAWA、Kazuyuki HORI、Toshio TANIYAMA、Jun-Liang ZHOU、Masayuki YOSHIKAWA

  DOI：10.1248/cpb.41.43

  日期：——

  From the air-dried root of Glycyrrhiza uralensis, collected in the northeastern part of China, ten new oleanane-type triterpene oligoglycosides were isolated together with glycyrrhizin (1) and several known flavonoids. Among the newly isolated triterpene oligoglycosides, the chemical structures of licorice-saponin A3 (2), licorice-saponin B2 (3), and licorice-saponin C2 (4) have been determined, on the basis of chemical and physicochemical evidence, to be expressed as 30-O-β-D-glucopyranosylglycyrrhizm, 11-deoxo-glycyrrhizin, and 3-O-[β-D-glucuronopyranosyl(1→2)-β-D-glucuronopyranosyl]oleana-11, 13(18)-dien-30-oic acid, respectively. During the course of these studies, facile conversions from glycyrrhizn (1) to licorice-saponins A3 (2), B2 (3), and C2 (4) have been accomplished.

  从中国东北地区采集的风干的乌拉尔甘草根中，分离出 10 种新的齐墩果烷型三萜寡糖苷以及甘草甜素 (1) 和几种已知的黄酮类化合物。在新分离的三萜低聚糖苷中，根据化学和理化证据，已确定甘草皂苷 A3 (2)、甘草皂苷 B2 (3) 和甘草皂苷 C2 (4) 的化学结构为表示为 30-O-β-D-吡喃葡萄糖基甘草酸、11-脱氧甘草酸，以及分别为3-O-[β-D-吡喃葡萄糖醛酸基(1→2)-β-D-吡喃葡萄糖醛酸基]oleana-11、13(18)-dien-30-oic酸。在这些研究过程中，已经实现了从甘草酸 (1) 到甘草皂苷 A3 (2)、B2 (3) 和 C2 (4) 的轻松转化。
• Solubilizing properties of glycyrrhizin and its derivatives: Solubilization of saikosaponin-a, the saponin of Bupleuri radix.
  作者：YASUHIRO SASAKI、KENJI MIZUTANI、RYOJI KASAI、OSAMU TANAKA

  DOI：10.1248/cpb.36.3491

  日期：——

  Licorice root is often co-prescribed with Bupleuri Radix (Bupleurum root) for decoctions used in oriental traditional medicine. It was found that the water solubility of saikosaponin-a, the active principle of Bupleurum root, was increased in the presence of the water extract or the saponin fraction of licorice root and this solubilizing effect was due to glycyrrhizin, the major active saponin of this plant drug. A solubilizing effect on saikosaponin-a was also observed with the 30-β-glucoside ester and 30-β-glucuronide ester of glycyrrhizin. The 30-β-glucoside ester improved the solubilizing property of glycyrrhizin. Aqueous solutions of the 30-β-glucoside ester and the 30-β-glucuronide ester solubilized dl-α-tocopherol and oleanolic acid, both of which are almost insoluble in water.

  在东方传统医学中，甘草根通常与柴胡（Bupleuri Radix，柴胡根）共同用于煎剂。研究发现，在甘草根的水提取物或皂甙部分存在的情况下，柴胡根的活性成分柴胡皂苷-a 的水溶性增加，这种增溶作用是由甘草苷（这种植物药的主要活性皂甙）引起的。甘草苷的 30-β- 葡萄糖苷酯和 30-β- 葡萄糖醛酸苷酯也对赛科皂甙-a 有增溶作用。30-β- 葡萄糖苷酯改善了甘草苷的增溶特性。30-β-Glucoside 酯和 30-β-Glucuronide 酯的水溶液可溶解几乎不溶于水的 dl-α-生育酚和齐墩果酸。
• Mannosylated saponins based on oleanolic and glycyrrhizic acids. Towards synthetic colloidal antigen delivery systems
  作者：Alison M. Daines、Ben W. Greatrex、Colin M. Hayman、Sarah M. Hook、Warren T. McBurney、Thomas Rades、Phillip M. Rendle、Ian M. Sims

  DOI：10.1016/j.bmc.2009.05.043

  日期：2009.7

  Immunostimulatory saponin based colloidal antigen delivery systems show promise as adjuvants for subunit vaccines. For this reason, allyl oleanolate was glycosylated at the 3-position using trichloroacetimidate donors to give monodesmodic saponins following deprotection. Bisdesmodic saponins were synthesized by double glycosylation at the 3- and 28-positions of oleanolic acid. When formulated together with cholesterol and phospholipids, ring-like, helical and rod-like nanostructures were formed depending on the saponin concentrations used. As an indication of adjuvant activity, the ability of these formulations, and the saponins by themselves, to induce dendritic cell maturation was measured, but no significant activity was observed. (C) 2009 Elsevier Ltd. All rights reserved.
• KITAGAWA, ISAO;ZHOU, JUN LIANG;SAKAGAMI, MASAHIRO;TANIYAMA, TOSHIO;YOSHIK+, CHEM. AND PHARM. BULL., 36,(1988) N 9, C. 3710-3713
  作者：KITAGAWA, ISAO、ZHOU, JUN LIANG、SAKAGAMI, MASAHIRO、TANIYAMA, TOSHIO、YOSHIK+

  DOI：——

  日期：——
• Synthesis, Biological Evaluation, and Molecular Modeling of Glycyrrhizin Derivatives as Potent High-Mobility Group Box-1 Inhibitors with Anti-Heart-Failure Activity in Vivo
  作者：Dan Du、Jun Yan、Jinhong Ren、Haining Lv、Yong Li、Song Xu、Yadan Wang、Shuanggang Ma、Jing Qu、Weibin Tang、Zhuowei Hu、Shishan Yu

  DOI：10.1021/jm301248y

  日期：2013.1.10

  Novel glycyrrhizin (GL) derivatives were designed and synthesized by introducing various amine or amino acid residues into the carbohydrate chain and at C-30. Their inhibitory effects on high-mobility group box 1 (HMGB1) were evaluated using a cell-based lipopolysaccharide (LPS) induced tumor necrosis factor alpha (TNF-alpha) release study. Compounds 10, 12, 18-20, 23, and 24, which had substituents introduced at C-30, demonstrated moderate HMGB1 inhibition with ED50 values ranging from 337 to 141 mu M, which are values comparable to that of the leading GL compound (1) (ED50 = 70 mu M). Compounds 23 and 24 emerged as novel and interesting HMGB1 inhibitors. These compounds were able to extend the survival of mice with chronic heart failure (CHF) and acute heart failure (AHF), respectively. In addition, molecular modeling studies were performed to support the biological data.