benzyl oleanolate 3-O-2,3,4-tri-O-benzoyl-α-L-arabinopyranoside | 875878-32-3

• 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: benzyl oleanolate 3-O-2,3,4-tri-O-benzoyl-α-L-arabinopyranoside
• 英文别名: benzyl 3-O-2,3,4-tri-O-benzoyl-α-L-arabinopyranosyloleanolate；benzyl (4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-2,2,6a,6b,9,9,12a-heptamethyl-10-[(2S,3R,4S,5S)-3,4,5-tribenzoyloxyoxan-2-yl]oxy-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylate
• CAS: 875878-32-3
• 化学式: C₆₃H₇₄O₁₀
• 分子量: 991.275
• InChiKey: QVAVLSDDASMECC-WHRJZMFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  14.5
• 重原子数：
  73
• 可旋转键数：
  15
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  benzyl oleanolate 3-O-2,3,4-tri-O-benzoyl-α-L-arabinopyranoside 在 4 A molecular sieve 、 三氟化硼乙醚 、 sodium methylate 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 丙酮 、 甲苯 为溶剂， 反应 6.0h， 生成 benzyl oleanolate 3-O-2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl-(1->2)-4-O-acetyl-α-L-arabinopyranoside
  参考文献：
  名称：

  Synthesis of β-hederin and Hederacolchiside A1: triterpenoid saponins bearing a unique cytotoxicity-inducing disaccharide moiety

  摘要：

  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.

  DOI：

  10.1016/j.carres.2005.10.015
• 作为产物：
  描述：

  L-(+)-arabinose 在 吡啶 、 三氟甲磺酸三甲基硅酯 、 水 、 氢溴酸 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 silver carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 6.0h， 生成 benzyl oleanolate 3-O-2,3,4-tri-O-benzoyl-α-L-arabinopyranoside
  参考文献：
  名称：

  EP3973965

  摘要：

  公开号：

文献信息

• Facile Synthesis of the Naturally Cytotoxic Triterpenoid Saponin Patrinia-Glycoside B-II and Its Conformer
  作者：Li Ren、Yong-Xiang Liu、Dan Lv、Mao-Cai Yan、Han Nie、Yang Liu、Mao-Sheng Cheng

  DOI：10.3390/molecules181215193

  日期：——

  The first chemical synthesis of the natural triterpenoid saponin Patrinia-glycoside B-II, namely oleanolic acid 3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-gluco-pyranosyl-(1→3)]-α-L-arabinopyranoside, has been accomplished in a linear 11-step sequence 11 with 9.4% overall yield. The abnormal 1C4 conformation of the arabinose residue was found to occur via conformational fluctuation during preparation of the intermediates. Molecular mechanism and quantum chemistry calculations showed that Patrinia-glycoside B-II and its conformer 1 cannot interconvert under normal conditions. Preliminary structure-activity relationships studies indicated that the 4C1 chair conformation of the arabinose residue in the unique α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl disaccharide moiety is one of the chief positive factors responsible for its cytotoxic activity against tumors.

  首次以线性 11 步序列 11 完成了天然三萜皂苷 Patrinia-glycoside B-II 即齐墩果酸 3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-Gluco-pyranosyl-(1→3)]-α-L-arabinopyranoside 的化学合成，总收率为 9.4%。研究发现，阿拉伯糖残基的异常 1C4 构象是在制备中间体的过程中通过构象波动产生的。分子机理和量子化学计算表明，在正常条件下，帕特里尼亚糖苷 B-II 及其构象 1 不能相互转化。初步的结构-活性关系研究表明，独特的α-L-吡喃鼠李糖基-(1→2)-α-L-阿拉伯吡喃糖基二糖分子中阿拉伯糖残基的 4C1 椅构象是其对肿瘤具有细胞毒性活性的主要积极因素之一。
• Synthesis and antitumor activity evaluation of oleanolic acid saponins bearing an acetylated l-arabinose moiety
  作者：Ye Zhong、Hui-ning Li、Lin Zhou、Hua-sheng Su、Mao-sheng Cheng、Yang Liu

  DOI：10.1016/j.carres.2021.108311

  日期：2021.5

  derivatives bearing acetyl-substituted l-arabinose moiety has been synthesized and screened in vitro for cytotoxicity against ten cancer cell lines and four normal cell lines. The antiproliferative evaluation indicated that synthetic derivatives showed excellent selectivity, as they were toxic against only A431 cell line. Among them, the compound 6 possesses the best inhibitory activity. A series of

  甲小号轴承乙酰基取代的齐墩果酸衍生物的eries升-arabinose部分已经合成和筛选体外针对10癌细胞系和四个正常细胞系的细胞毒性。抗增殖评估表明合成衍生物显示出极好的选择性，因为它们仅对 A431 细胞系有毒。其中，化合物6具有最好的抑制活性。一系列药理实验表明，化合物6显着诱导A431细胞凋亡和细胞周期阻滞，可作为进一步研究的潜在先导候选物。
• Facile Synthesis of Oleanolic Acid Monoglycosides and Diglycosides
  作者：Yu Sha、Mao-Cai Yan、Jiao Liu、Yang Liu、Mao-Sheng Cheng

  DOI：10.3390/molecules13071472

  日期：——

  condensation of the carboxylic acid with bromo-glycosides was found to be more efficient in the synthesis of 28-glycosides. Two approaches were investigated and proved practicable in the preparation of 3,28- diglycosides. This method is suitable for preparing oleanolic acid glycosides with structural diversity for extensive biological evaluation and structure-activity relationship study, and it also apply new

  齐墩果酸及其苷类是重要的天然产物，具有多种有吸引力的生物活性，如抗肿瘤、抗病毒和抗炎特性。在目前的工作中，15 种带有各种糖基的齐墩果酸皂苷，包括 3-单糖苷、28-单糖苷和 3,28-二糖苷，很容易以高产率合成。选择苄基作为 COOH(28) 基团的保护基团，而不是常用的甲基和烯丙基，以避免最终脱保护的困难。发现碱促进羧酸与溴糖苷的缩合在 28-糖苷的合成中更有效。研究了两种方法并证明在制备 3,28-二糖苷中是可行的。
• Synthesis and Biological Evaluation of Raddeanin A, a Triterpene Saponin Isolated from <i>Anemone raddeana</i>
  作者：Shan Qian、Quan Long Chen、Jin Long Guan、Yong Wu、Zhou Yu Wang

  DOI：10.1248/cpb.c14-00138

  日期：——

  First, Raddeanin A, a cytotoxic oleanane-type triterpenoid saponin isolated from Anemone raddeana REGEL, was synthesized. Stepwise glycosylation was adopted in the synthesis from oleanolic acid, employing arabinosyl, glucosyl and rhamnosyl trichloroacetimidate as donors. The chemical structure of Raddeanin A was confirmed by means of 1H-NMR, 13C-NMR, IR, MS and elemental analysis, which elucidated the structure to be 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside oleanolic acid. Biological activity tests showed that in the range of low concentrations, Raddeanin A displayed moderate inhibitory activity against histone deacetylases (HDACs), indicating that the HDACs’ inhibitory activity of Raddeanin A may contribute to its cytotoxicity.

  首先，合成了一种具有细胞毒性的齐墩果酸类三萜皂甙 Raddeanin A，它是从 Anemone raddeana REGEL 中分离出来的。以齐墩果酸为原料，以阿拉伯糖基、葡萄糖基和鼠李糖基三氯乙酰亚氨酸为供体，采用逐步糖基化的方法进行合成。通过 1H-NMR、13C-NMR、IR、MS 和元素分析确认了 Raddeanin A 的化学结构，阐明其结构为 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside oleanolic acid。生物活性测试表明，在低浓度范围内，Raddeanin A 对组蛋白去乙酰化酶（HDACs）具有中等程度的抑制活性，这表明 Raddeanin A 的 HDACs 抑制活性可能是其细胞毒性的原因之一。
• Synthesis and Tumor Cytotoxicity of Novel Amide Derivatives of β-Hederin
  作者：Yang Liu、Wen-Xiang Lu、Mao-Cai Yan、Yang Yu、Takashi Ikejima、Mao-Sheng Cheng

  DOI：10.3390/molecules15117871

  日期：——

  Thirteen novel triterpenoid saponins, designed as amide derivatives of the natural cytotoxic saponin β-hederin, were synthesized by a stepwise glycosylation strategy. The in vitro cytotoxic activity of these compounds was evaluated against five different tumor cell lines. Most of the evaluated compounds showed effective inhibitory activity against at least one tumor cell line at micromolar concentrations. The preliminary structure-activity relationships (SAR) indicate that mide derivatization at C-28 resulted in highly cytotoxic derivatives on specific tumor cell lines, and also resulted in an increase in the antitumor selectivity of β-hederin.

  通过逐步糖基化策略合成了 13 种新型三萜皂苷，设计为天然细胞毒性皂苷 β-常春藤素的酰胺衍生物。针对五种不同的肿瘤细胞系评估了这些化合物的体外细胞毒活性。大多数评估的化合物在微摩尔浓度下对至少一种肿瘤细胞系表现出有效的抑制活性。初步的构效关系（SAR）表明，C-28位点的mide衍生化产生了对特定肿瘤细胞系具有高度细胞毒性的衍生物，并且还导致β-常春藤素的抗肿瘤选择性增加。