黑海常春藤皂苷A1 | 106577-39-3

• 物质功能分类: 生物化工 - 提取物 - 植物提取物
• 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
• 中文名称: 黑海常春藤皂苷A1
• 中文别名: 竹节香附皂苷R13；HEDERACOLCHISIDEA1(标准品)；齐墩果酸-3-O-Β-D-吡喃鼠李糖基-(1→2)-[Β-D-吡喃葡萄糖基-(1→4)]-Α-L-吡喃阿拉伯糖苷；齐墩果酸-3-O-Β-D-吡喃鼠李糖基-(1→2)-Β-D-吡喃葡萄糖基-(1→4)-Α-L-吡喃阿拉伯糖苷；黑海常春藤苷A1；齐墩果酸-3-O-Α-L鼠李吡喃糖基-(1→2)[Β-D-葡萄吡喃糖基-(1→4)]-Α-L-吡喃阿拉伯糖苷；革叶常春藤皂苷A1
• 英文名称: 3β-O-{α-L-rhamnopyranosyl-(1->2)-[β-D-glucopyranosyl-(1->4)]-α-L-arabinopyranosyl}oleanolic acid
• 英文别名: oleanolic acid 3-O-{O-α-L-rhamnopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→4)]-α-L-arabinopyranoside}；oleanolic acid 3-O-[α-L-rhamnopyranosyl-(1->2)-[β-D-glucopyranosyl-(1->4)]-α-L-arabinopyranoside]；oleanoic acid 3-O-α-L-rhamnopyranosyl-(1->2)-[O-β-D-glucopyranosyl-(1->4)]-α-L-arabinopyranoside；oleanolic acid 3-O-α-L-rhamnopyranosyl-(1->2)-[β-D-glucopyranosyl-(1->4)]-α-L-arabinopyranoside；3-O-{[β-D-glucopyranosyl(1→4)]-[α-L-rhamnopyranosyl-(1→2)]-α-L-arabinopyranosyl}oleanolic acid；oleanolic acid 3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-α-L-arabinopyranoside；Hederacolchiside A1；(4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-[(2S,3R,4S,5S)-4-hydroxy-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid
• CAS: 106577-39-3
• 化学式: C₄₇H₇₆O₁₆
• 分子量: 897.111
• InChiKey: FYSAXYBPXKLMJO-IFECXJOTSA-N

物化性质

• 熔点：
  253-255℃ (methanol , water )
• 沸点：
  967.2±65.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  63
• 可旋转键数：
  8
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  255
• 氢给体数：
  9
• 氢受体数：
  16

安全信息

• WGK Germany：
  3

制备方法与用途

生物活性

Hederacolchiside A1是从白头翁中分离出的一种化合物，通过调节PI3K/Akt/mTOR信号通路诱导凋亡，从而抑制肿瘤细胞的增殖。此外，它还具有抗血吸虫病活性，能够影响体内和体外寄生虫的生存力。

靶点

• PI3K
• Akt
• mTOR

体外研究

Hederacolchiside A1能降低线粒体膜电位并减少Bcl-2蛋白水平，同时增加cleaved caspase-3的表达。此外，它还能有效抑制磷脂酰肌醇3激酶（PI3K）、蛋白质激酶B（Akt）和哺乳动物雷帕霉素靶点（mTOR）的磷酸化。

体内研究

Hederacolchiside A1在不同剂量下（3.0, 4.5, 和6.0 mg/kg，腹腔注射）能显著抑制H22异种移植肿瘤模型中的肿瘤重量。同样，在裸鼠中使用人乳腺癌MCF-7细胞建立的异种移植肿瘤模型中，Hederacolchiside A1在不同剂量下（3.25, 7.5, 和15.0 mg/kg，灌胃）也能显著抑制肿瘤重量。

反应信息

• 作为反应物：
  描述：

  3-溴丙酸 、 黑海常春藤皂苷A1 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以59%的产率得到3-[(4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-[(2S,3R,4S,5S)-4-hydroxy-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]oxypropanoic acid
  参考文献：
  名称：

  菊苣苷A1衍生物作为抗癌剂的合成及生物学评价。

  摘要：

  在28-COOH上修饰七叶树胶苷A1（HA1），得到一系列含有酯基或酰胺基的新型三萜皂苷化合物。与天然产物HA1相比，几种衍生物在小鼠急性毒性试验中显示出较低的毒性，并在体外具有增强的抗癌活性。特别是化合物1对测试的人类癌细胞系表现出最强的抗增殖活性（IC50 =1.1-4.6μM），体内的有效肿瘤抑制率（46.8％）。

  DOI：

  10.1016/j.bmcl.2016.08.077
• 作为产物：
  描述：

  oleanolic acid 3-O-2,3,4-tri-O-acetyl-α-L-rhamnopyranosyl-(1→2)-[2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl-(1→4)]-α-L-arabinopyranoside 在 sodium methylate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 黑海常春藤皂苷A1
  参考文献：
  名称：

  Synthesis, biological evaluation and structure-activity relationship studies of hederacolchiside E and its derivatives as potential anti-Alzheimer agents

  摘要：

  Inspired by the previously reported neuroprotective activity of hederacolchiside E (1), we synthesized hederacolchiside E for the first time along with eleven of its derivatives. The neuroprotective effects of these compounds were further evaluated against H2O2- and A beta(1-42)-induced injury using cell-based assays. The derivatives showed obvious differences in activity due to structural variations, and two of them exhibited better neuroprotective effects than 1 in the A beta(1-42)-induced injury model. Compound 7 was the most active derivative and had a relatively simple chemical structure. Moreover, 1 and 7 can significantly reduce the release of lactate dehydrogenase (LDH), level of intracellular reactive oxygen species (ROS) and extent of malondialdehyde (MDA) increase resulting from A beta(1-42) treatment, which demonstrated that these kinds of compounds show neuroprotective effects in Alzheimer's disease (AD) models via modulating oxidative stress. Compound 7 could be used as promising lead for the development of a new type of neuroprotective agent against AD. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.11.040

文献信息

• Nitric oxide-donating derivatives of hederacolchiside A 1 : Synthesis and biological evaluation in vitro and in vivo as potential anticancer agents
  作者：Yuanying Fang、Rikang Wang、Mingzhen He、Hesong Huang、Qi Wang、Zunhua Yang、Yan Li、Shilin Yang、Yi Jin

  DOI：10.1016/j.bmcl.2016.11.021

  日期：2017.1

  A series of nitric oxide (NO) donating derivatives of hederacolchiside A1 bearing triterpenoid saponin motif were designed, synthesized and evaluated for their anticancer activity. All of the tested furoxan-based NO releasing compounds showed significant proliferation inhibitory activities. Especially compound 6a exhibited strong cytotoxicity (IC50=1.6-6.5μM) against four human tumor cell lines (SMMC-7721

  设计，合成和评估了一系列带有三萜皂苷基序的二十碳五烯苷A1的一氧化氮（NO）捐赠衍生物。所有测试的基于呋喃喃的NO释放化合物均显示出显着的增殖抑制活性。尤其是化合物6a在体外对四种人类肿瘤细胞系（SMMC-7721，NCI-H460，U251，HCT-116）表现出强大的细胞毒性（IC50 =1.6-6.5μM），并具有最高水平的NO释放。此外，化合物6a显示出对小鼠的低急性毒性和弱的溶血活性，并且在体内对小鼠H22肝细胞具有有效的肿瘤生长抑制作用（51.5％）。
• Synthesis of β-hederin and Hederacolchiside A1: triterpenoid saponins bearing a unique cytotoxicity-inducing disaccharide moiety
  作者：Mao-Sheng Cheng、Mao-Cai Yan、Yang Liu、Li-Gang Zheng、Jiao Liu

  DOI：10.1016/j.carres.2005.10.015

  日期：2006.1

  A facile synthetic approach toward oleanolic acid glycoside bearing alpha-L-rhamnopyranosyl-(1 -> 2)-alpha-L-arabinopyranosyl moiety, a unique oligosaccharide that strongly induces antitumor activity of oleanane-type triterpenoid saponins, was developed. Based on this approach P-hederin (oleanolic acid 3-0-Gt-L-rhamnopyranosyl-(1 -> 2)-alpha- L-arabinopyrano side) was efficiently prepared from oleanolic acid through stepwise glycosylation in linear eight steps with 52% overall yield, while Hederacolchiside A, (oleanolic acid 3-O-alpha-L-rhamnopyranosyl-(1 -> 2)-[beta-D-glucopyranosyl-(1 -> 4)]-alpha-L-arabinopyranoside) in linear 13 steps with 20% overall yield. (c) 2005 Published by Elsevier Ltd.
• Facile synthesis and cytotoxicity of triterpenoid saponins bearing a unique disaccharide moiety: hederacolchiside A1 and its analogues
  作者：Mao-Cai Yan、Yang Liu、Wen-Xiang Lu、Hui Wang、Yu Sha、Mao-Sheng Cheng

  DOI：10.1016/j.carres.2007.12.014

  日期：2008.3

  An improved synthetic approach toward hederacolchiside A(1), an antitumor triterpenoid saponin bearing a unique disaccharide moiety, was established. This approach began from a partially protected intermediate and avoided tedious protection-deprotection manipulation. An abnormal ring conformation ((1)C(4)) of the center arabinose residue was found in the intermediate, which may account for the unusual regioselectivity between 3-OH and 4-OH of arabinose. Two analogues of hederacolchiside A(1) were then facilely prepared by this approach and exhibited significant cytotoxicity in preliminary in vitro assay. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis, biological evaluation and structure-activity relationship studies of hederacolchiside E and its derivatives as potential anti-Alzheimer agents
  作者：Hui-ning Li、Yang Liu、Zuo-peng Zhang、Zhi-peng Wang、Jing-zheng Hao、Feng-ran Li、Zhan-fang Fan、Li-bo Zou、Mao-sheng Cheng

  DOI：10.1016/j.ejmech.2017.11.040

  日期：2018.1

  Inspired by the previously reported neuroprotective activity of hederacolchiside E (1), we synthesized hederacolchiside E for the first time along with eleven of its derivatives. The neuroprotective effects of these compounds were further evaluated against H2O2- and A beta(1-42)-induced injury using cell-based assays. The derivatives showed obvious differences in activity due to structural variations, and two of them exhibited better neuroprotective effects than 1 in the A beta(1-42)-induced injury model. Compound 7 was the most active derivative and had a relatively simple chemical structure. Moreover, 1 and 7 can significantly reduce the release of lactate dehydrogenase (LDH), level of intracellular reactive oxygen species (ROS) and extent of malondialdehyde (MDA) increase resulting from A beta(1-42) treatment, which demonstrated that these kinds of compounds show neuroprotective effects in Alzheimer's disease (AD) models via modulating oxidative stress. Compound 7 could be used as promising lead for the development of a new type of neuroprotective agent against AD. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Synthesis and biological evaluation of Hederacolchiside A 1 derivatives as anticancer agents
  作者：Yuanying Fang、Zunhua Yang、Hui Ouyang、Rikang Wang、Jun Li、Hesong Huang、Yi Jin、Yulin Feng、Shilin Yang

  DOI：10.1016/j.bmcl.2016.08.077

  日期：2016.10

  A1 (HA1) on 28-COOH gave a series of novel triterpenoid saponin compounds containing ester or amide group. Comparing with natural product HA1, several derivatives showed decreased toxicity in the mice acute toxicity trial and increased the anticancer activity in vitro. Especially compound 1 exhibited the strongest antiproliferative activities against human cancer cell lines tested (IC50=1.1-4.6μM) and

  在28-COOH上修饰七叶树胶苷A1（HA1），得到一系列含有酯基或酰胺基的新型三萜皂苷化合物。与天然产物HA1相比，几种衍生物在小鼠急性毒性试验中显示出较低的毒性，并在体外具有增强的抗癌活性。特别是化合物1对测试的人类癌细胞系表现出最强的抗增殖活性（IC50 =1.1-4.6μM），体内的有效肿瘤抑制率（46.8％）。