3β-hydroxy-N-benzylolean-12-en-28-amide | 1079338-67-2

• 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-hydroxy-N-benzylolean-12-en-28-amide
• 英文别名: Benzyl oleanolic acid amide；(4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-N-benzyl-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxamide；(4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-N-benzyl-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxamide
• CAS: 1079338-67-2
• 化学式: C₃₇H₅₅NO₂
• 分子量: 545.849
• InChiKey: YWXYIQJXIIUZMR-GBVPUKILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  40
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3β-hydroxy-N-benzylolean-12-en-28-amide 在 氨基磺酰氯 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 以86 %的产率得到(3β)-[(aminosulfonyl)oxy]-N-benzylolean-12-en-28-amide
  参考文献：
  名称：

  积雪草酸衍生的三氨基磺酸盐作为人碳酸酐酶 VA 的纳摩尔抑制剂

  摘要：

  这项研究深入研究了一组特定的三萜酸对人碳酸酐酶 (CA) 不同亚型的抑制能力。选择齐墩果酸()、山楂酸()、桦木酸()、铂酸()和积雪草酸()作为代表性三萜类化合物进行评价。合成过程涉及母体三萜酸的乙酰化，然后与草酰氯和苄胺连续反应，酰胺脱乙酰化，随后用氢化钠和氨磺酰氯处理，形成最终化合物。

  DOI：

  10.1016/j.steroids.2024.109381
• 作为产物：
  描述：

  齐墩果酸 在 甲醇 、 4-二甲氨基吡啶 、 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 、 potassium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 28.0h， 生成 3β-hydroxy-N-benzylolean-12-en-28-amide
  参考文献：
  名称：

  积雪草酸衍生的三氨基磺酸盐作为人碳酸酐酶 VA 的纳摩尔抑制剂

  摘要：

  这项研究深入研究了一组特定的三萜酸对人碳酸酐酶 (CA) 不同亚型的抑制能力。选择齐墩果酸()、山楂酸()、桦木酸()、铂酸()和积雪草酸()作为代表性三萜类化合物进行评价。合成过程涉及母体三萜酸的乙酰化，然后与草酰氯和苄胺连续反应，酰胺脱乙酰化，随后用氢化钠和氨磺酰氯处理，形成最终化合物。

  DOI：

  10.1016/j.steroids.2024.109381

文献信息

• MSBA-S – A pentacyclic sulfamate as a new option for radiotherapy of human breast cancer cells
  作者：Marina Petrenko、Antje Güttler、Elena Pflüger、Immo Serbian、Michael Kahnt、Yvonne Eiselt、Jacqueline Keßler、Anne Funtan、Reinhard Paschke、René Csuk、Dirk Vordermark、Matthias Bache

  DOI：10.1016/j.ejmech.2021.113721

  日期：2021.11

  triterpenoids show anti-cancer and anti-inflammatory properties. Recently, we detected a pronounced cytotoxicity and radiosensitivity of two betulinyl sulfamates in human breast cancer cells. Besides betulinic acid scaffold (BSBA-S), we synthesized several new sulfamate-coupled scaffolds from oleanolic acid (OSBA-S), ursolic acid (USBA-S), platanic acid (PSBA-S) and maslinic acid (MSBA-S). Highest cytotoxicity

  许多五环三萜类化合物具有抗癌和抗炎特性。最近，我们在人类乳腺癌细胞中检测到两种氨基磺酸白桦脂酸酯具有明显的细胞毒性和放射敏感性。除了桦木酸支架（BSBA-S），我们还合成了齐墩果酸（OSBA-S）、熊果酸（USBA-S）、铂酸（PSBA-S）和山楂酸（MSBA-S）几种新的氨基磺酸盐偶联支架。 . 在 MSBA-S 处理后，在乳腺癌细胞系中监测到最高的细胞毒性，在 SRB 测定中显示，IC 50值介于 3.7 μM 和 5.8 μM 之间。然而，其他氨基磺酸盐/三萜偶联物的细胞毒性较小，IC 50值分别在 6.6 μM 和 >50 μM 之间。MSBA- S与其他缀合物相比，经处理的乳腺癌细胞表现出显着降低的克隆形成存活率和增加的细胞凋亡率。此外，MSBA-S 与辐射相结合对 MDA-MB-231 细胞的放射敏感性产生影响（DMF 10  = 1.14）。特别是，在 MSBA- S处理的乳腺癌细胞中强烈评估了
• Targeting mitochondria: Esters of rhodamine B with triterpenoids are mitocanic triggers of apoptosis
  作者：Ratna Kancana Wolfram、Lucie Heller、René Csuk

  DOI：10.1016/j.ejmech.2018.04.031

  日期：2018.5

  Triterpenoic acids, ursolic acid (1), oleanolic acid (2), glycyrrhetinic acid (3) and betulinic acid (4) were converted into their corresponding methyl 5-8 and benzyl esters 9-12 or benzyl amides 21-24. These derivatives served as starting materials for the synthesis of pink colored rhodamine B derivatives 25-36 which were screened for cytotoxicity in colorimetric SRB assays. All of the compounds were

  将三萜酸，熊果酸（1），齐墩果酸（2），甘草次酸（3）和桦木酸（4）转化为其相应的甲基5-8和苄基酯9-12或苄基酰胺21-24。这些衍生物用作合成粉红色若丹明B衍生物25-36的起始材料，在比色SRB分析中筛选了细胞毒性。所有这些化合物对多种人类肿瘤细胞系均具有细胞毒性。苄基酯衍生物29-32的活性低于甲基酯25-28的细胞毒性。苄基酰胺33-36是该系列中最具细胞毒性的化合物。最有潜力的化合物是甘草次酸罗丹明B苄基酰胺35。该化合物对不同癌细胞系的活性在2位数至3位数的低纳摩尔范围内。
• Oleanolic acid and its derivatives: New inhibitor of protein tyrosine phosphatase 1B with cellular activities
  作者：Yi-Nan Zhang、Wei Zhang、Di Hong、Lei Shi、Qiang Shen、Jing-Ya Li、Jia Li、Li-Hong Hu

  DOI：10.1016/j.bmc.2008.07.080

  日期：2008.9

  Protein tyrosine phosphatase 1B is a key factor in the negative regulation of insulin pathway and a promising target for treatment of diabetes and obesity. Herein, a series of competitive inhibitors were optimized from oleanolic acid, a natural triterpenoid identified against PTP1B by screening libraries of traditional Chinese medicinal herbs. Modifying at 3 and 28 positions, we obtained compound 13

  酪氨酸磷酸酶1B蛋白是胰岛素通路负调节的关键因素，也是治疗糖尿病和肥胖症的有希望的靶标。本文中，通过筛选传统中草药文库中鉴定出的针对PTP1B的天然三萜类化合物齐墩果酸，优化了一系列竞争性抑制剂。在3和28位上进行修饰，我们获得了K（i）为130 nM的化合物13，该化合物在除T细胞蛋白酪氨酸磷酸酶以外的其他与胰岛素途径有关的磷酸酶之间表现出良好的选择性。在细胞模型中的进一步评估表明，这些衍生物增强了CHO / hIR细胞中胰岛素受体的磷酸化作用，并刺激了添加或不添加胰岛素的L6肌管中的葡萄糖摄取。
• Towards cytotoxic and selective derivatives of maslinic acid
  作者：Bianka Siewert、Elke Pianowski、Anja Obernauer、René Csuk

  DOI：10.1016/j.bmc.2013.10.047

  日期：2014.1

  Several novel esters and amides of maslinic acid were prepared. Their evaluation for cytotoxic activity with a panel of human cancer cell lines using a sulforhodamine B (SRB) assay revealed for some of them a noteworthy activity. The results from annexinV-FITC and caspase-assays as well as from DNA laddering experiments provided evidence for an apoptotic cell death. A diacetylated benzylamide (15) induced a G1/G0 arrest in tumor cells. It also displayed an extraordinary cytotoxicity against human ovarian cancer cells but a 300 times lower toxicity for non-malignant primary human fibroblasts. (C) 2013 Elsevier Ltd. All rights reserved.
• Rational design and synthesis of topoisomerase I and II inhibitors based on oleanolic acid moiety for new anti-cancer drugs
  作者：Ahmed Ashour、Saleh El-Sharkawy、Mohamed Amer、Fatma Abdel Bar、Yoshinori Katakura、Tomofumi Miyamoto、Nozomi Toyota、Tran Hai Bang、Ryuichiro Kondo、Kuniyoshi Shimizu

  DOI：10.1016/j.bmc.2013.11.034

  日期：2014.1

  Semisynthetic reactions were conducted on oleanolic acid, a common plant-derived oleanane-type triterpene. Ten rationally designed derivatives of oleanolic acid were synthesized based on docking studies and tested for their topoisomerase I and IIa inhibitory activity. Semisynthetic reactions targeted C-3, C-12, C-13, and C-17. Nine of the synthesized compounds were identified as new compounds. The structures of these compounds were confirmed by spectroscopic methods (1D, 2D NMR and MS). Five oleanolic acid analogues (S2, S3, S5, S7 and S9) showed higher activity than camptothecin (CPT) in the topoisomerase I DNA relaxation assay. Four oleanolic acid analogues (S2, S3, S5 and S6) showed higher activity than etoposide in a topoisomerase II assay. The results indicated that the C12-C13 double bond of the oleanolic acid skeleton is important for the inhibitory activity against both types of topoisomerases, while insertion of a longer chain at either position 3 or 17 increases the activity against topoisomerases by various degrees. Some of the synthesized compounds act as dual inhibitors for both topoisomerase I and IIa. (C) 2013 Elsevier Ltd. All rights reserved.