3-O-(2′-nonanoylamino-2′-deoxy-β-D-glucopyranosyl)oleanolic 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: 3-O-(2′-nonanoylamino-2′-deoxy-β-D-glucopyranosyl)oleanolic acid
• 英文别名: (4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-[(2R,3R,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-(nonanoylamino)oxan-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
• 化学式: C₄₅H₇₅NO₈
• 分子量: 758.092
• InChiKey: GQSJJVRBDHNEGL-XGNVZUMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.4
• 重原子数：
  54
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-O-(2′-nonanoylamino-2′-deoxy-β-D-glucopyranosyl)oleanolic acid 、 炔丙胺 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 sodium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 以54%的产率得到28-N-propargyl-3-O-(2′-nonanoylamino-2′-deoxy-β-D-glucopyranosyl)oleanenamide
  参考文献：
  名称：

  Synthesis, distribution analysis and mechanism studies of N-acyl glucosamine-bearing oleanolic saponins

  摘要：

  A series of N-acyl glucosamine-bearing triterpenoid saponins has been synthesized with cytotoxic activities evaluated against HL-60, PC-3, HCT-116, and CT-26 tumor cells. Saponins incorporated an oleanolic acid (OA) triterpenoidal core exhibited the highest cytotoxic activity. To study the influence of the lengths of acyl-carbon chain on N-position of glucosamine, cells were treated with 28-propargylamides and then reacted with an azidofluorogenic probe under CuAAC click reactions to visualize the intact distributions of these compounds by confocal microscopy and flow cytometry; it was found that cytotoxic-active compounds (30-32) located in the cytosol and inactive compounds bearing longer carbon chains (33-35) were impenetrable across cell membranes. Our study demonstrated the defined lipophilic acyl-carbon chain length can precisely regulate the cytotoxic activity of saponins, which is useful for the future development of cytotoxic agents. Furthermore, using quantitative proteomics and immunolabeling, the mechanism of cytotoxicity induced by the synthetic saponin after membrane penetration could be a result of activation of death receptor pathway and inhibition of PI3K/Akt/mTOR pathway.

  DOI：

  10.1016/j.bioorg.2020.103835
• 作为产物：
  描述：

  p-methylphenyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside 在 N-溴代丁二酰亚胺(NBS) 、 三氟甲磺酸三甲基硅酯 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 乙二胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 31.0h， 生成 3-O-(2′-nonanoylamino-2′-deoxy-β-D-glucopyranosyl)oleanolic acid
  参考文献：
  名称：

  N-氨基葡萄糖修饰的齐墩果皂苷的设计，合成及细胞毒活性

  摘要：

  合成了一系列带有2'-脱氧葡萄糖基的齐墩果皂苷的N-酰基，N-烷氧基羰基和N-烷基氨基甲酰基衍生物，并针对HL-60，PC-3和HT29肿瘤癌细胞进行了评估。SAR研究表明，活性按氨基甲酸酯>酰胺>尿素衍生物与2'-氨基结合的顺序增加。延长烷基链可增加细胞毒性，发现其最高活性约为庚基至壬基取代。发现2'- N-庚氧基羰基衍生物56具有最高的细胞毒性（IC 50 = HL-60细胞的0.76μM）。由于烷基取代的SAR有趣，我们假设它们在细胞中的位置不同，并使用2'-（4''-戊炔基氨基）2'-脱氧-葡萄糖基OA进行了定位研究，这表明这些化合物主要分布在细胞质中

  DOI：

  10.1016/j.ejmech.2017.11.004

文献信息

• Design, synthesis and cytotoxic activity of N-Modified oleanolic saponins bearing A glucosamine
  作者：You-Yu Lin、She-Hung Chan、Yu-Pu Juang、Hsin-Min Hsiao、Jih-Hwa Guh、Pi-Hui Liang

  DOI：10.1016/j.ejmech.2017.11.004

  日期：2018.1

  A series of N-acyl, N-alkoxycarbonyl, and N-alkylcarbamoyl derivatives of 2′-deoxy-glucosyl bearing oleanolic saponins were synthesized and evaluated against HL-60, PC-3, and HT29 tumor cancer cells. The SAR studies revealed that the activity increased in order of conjugation of 2′ -amino group with carbamate > amide > urea derivatives. Lengthening the alkyl chain increased the cytotoxicity, the peak

  合成了一系列带有2'-脱氧葡萄糖基的齐墩果皂苷的N-酰基，N-烷氧基羰基和N-烷基氨基甲酰基衍生物，并针对HL-60，PC-3和HT29肿瘤癌细胞进行了评估。SAR研究表明，活性按氨基甲酸酯>酰胺>尿素衍生物与2'-氨基结合的顺序增加。延长烷基链可增加细胞毒性，发现其最高活性约为庚基至壬基取代。发现2'- N-庚氧基羰基衍生物56具有最高的细胞毒性（IC 50 = HL-60细胞的0.76μM）。由于烷基取代的SAR有趣，我们假设它们在细胞中的位置不同，并使用2'-（4''-戊炔基氨基）2'-脱氧-葡萄糖基OA进行了定位研究，这表明这些化合物主要分布在细胞质中
• Synthesis, distribution analysis and mechanism studies of N-acyl glucosamine-bearing oleanolic saponins
  作者：Yu-Pu Juang、You-Yu Lin、She-Hung Chan、Chun-Kai Chang、Jiun-Jie Shie、Yves S.Y. Hsieh、Jih-Hwa Guh、Pi-Hui Liang

  DOI：10.1016/j.bioorg.2020.103835

  日期：2020.6

  A series of N-acyl glucosamine-bearing triterpenoid saponins has been synthesized with cytotoxic activities evaluated against HL-60, PC-3, HCT-116, and CT-26 tumor cells. Saponins incorporated an oleanolic acid (OA) triterpenoidal core exhibited the highest cytotoxic activity. To study the influence of the lengths of acyl-carbon chain on N-position of glucosamine, cells were treated with 28-propargylamides and then reacted with an azidofluorogenic probe under CuAAC click reactions to visualize the intact distributions of these compounds by confocal microscopy and flow cytometry; it was found that cytotoxic-active compounds (30-32) located in the cytosol and inactive compounds bearing longer carbon chains (33-35) were impenetrable across cell membranes. Our study demonstrated the defined lipophilic acyl-carbon chain length can precisely regulate the cytotoxic activity of saponins, which is useful for the future development of cytotoxic agents. Furthermore, using quantitative proteomics and immunolabeling, the mechanism of cytotoxicity induced by the synthetic saponin after membrane penetration could be a result of activation of death receptor pathway and inhibition of PI3K/Akt/mTOR pathway.