methyl 3,11-dioxours-12-en-24-oate | 106455-64-5

• 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: methyl 3,11-dioxours-12-en-24-oate
• 英文别名: methyl (4β)-3,11-dioxo-urs-12-en-24-oate；(4β)-methyl 3,11-dioxours-12-en-24-oate；methyl 3,11-diketo-β-boswellic acid；3.11-dioxo-ursen-(12)-oic acid-(24)-methyl ester；3.11-Dioxo-ursen-(12)-saeure-(24)-methylester；methyl (4R,4aR,6aR,6bS,8aR,11R,12S,12aR,14aR,14bS)-4,6a,6b,8a,11,12,14b-heptamethyl-3,14-dioxo-2,4a,5,6,7,8,9,10,11,12,12a,14a-dodecahydro-1H-picene-4-carboxylate
• CAS: 106455-64-5
• 化学式: C₃₁H₄₆O₄
• 分子量: 482.704
• InChiKey: GQODJFGSPBYJJF-XKVIHBILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  35
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3,11-dioxours-12-en-24-oate 在 selenium(IV) oxide 、 乙酸酐 作用下， 反应 14.0h， 以78%的产率得到methyl (4β)-3,11-dioxo-urs-1,12-dien-24-oate
  参考文献：
  名称：

  Oxidative and reductive transformations of 11-keto-β-boswellic acid

  摘要：

  Extraction of frankincense-a fragrant resin obtained from plants of the genus Boswellia followed by an oxidation furnished high yields of (313) 3-O-acetyl-11-keto-beta-boswellic acid (beta-AKBA), a valuable starting material for accessing boswellic acid derivatives. Boswellic acids are fascinating triterpenoic acids that exhibit different biological activities. However, their biological potential, as well as that of their derivatives, remained unexploited due to their limited availability. In this study we were able to prepare derivatives of 11-keto-beta-boswellic acid in good to excellent yields by oxidative and reductive transformations mainly in rings A and C of the triterpenoid skeleton. Among other transformations, a highly cytotoxic endoperoxide was obtained in excellent yields. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.01.062
• 作为产物：
  描述：

  乙酰基-11-酮基-beta-乳香酸 在 Jones reagent 、 potassium carbonate 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 10.0h， 生成 methyl 3,11-dioxours-12-en-24-oate
  参考文献：
  名称：

  作为潜在抗 GBM 药物的新型乙酰基-11-酮-β-乳香酸衍生物的合成

  摘要：

  乙酰-11-酮-β-乳香酸 (AKBA) 已知可抑制胶质母细胞瘤 (GBM) 细胞和皮下 GBM 的生长。合成了一系列含有肟酯官能团或酰胺侧链的乙酰基-11-酮-β-乳香酸（AKBA）衍生物，并评估了它们的抗GBM活性。其中一些化合物对 U87 和 U251 GBM 细胞系中的细胞增殖表现出显着的抑制活性，IC 50值在微摩尔浓度范围内。细胞热位移分析表明A-01和A-10提高了FOXM1的热稳定性，表明这些高活性化合物可能直接与细胞内的FOXM1结合。对两种最活跃的化合物A-01和A-10的对接研究揭示了这些化合物与 FOXM1 活性位点之间的关键相互作用，其中 C-24 位点的酰胺部分对于提高活性至关重要。这些结果表明A-10是开发 FOXM1 抑制剂的合适先导分子。因此，合理设计具有酰胺侧链的AKBA衍生物对于发现一类能够抑制GBM细胞增殖的新型三萜类化合物具有巨大的潜力。

  DOI：

  10.1002/cbdv.202301979

文献信息

• Design, synthesis and biological evaluation of ring A modified 11-keto-boswellic acid derivatives as Pin1 inhibitors with remarkable anti-prostate cancer activity
  作者：Min Huang、Aihua Li、Feng Zhao、Xiaorui Xie、Kun Li、Yongkui Jing、Dan Liu、Linxiang Zhao

  DOI：10.1016/j.bmcl.2018.08.021

  日期：2018.10

  mitosis A1) is a validated molecular target for anticancer drug discovery. Herein, we reported the design, synthesis, and structure-activity relationship study of novel ring A modified AKBA (3-acetyl-11-keto-boswellic acid) derivatives as Pin1 inhibitors. Most compounds showed superior Pin1 inhibitory activities to AKBA. One of the most promising compounds, 10a, potently inhibited Pin1 with IC50 value

  Pin1（蛋白质在有丝分裂A1中从未相互作用）是经过验证的抗癌药物分子靶标。在本文中，我们报道了作为Pin1抑制剂的新型A环修饰的AKBA（3-乙酰基-11-酮-乳香酸）衍生物的设计，合成和构效关系研究。大多数化合物显示出优于AKBA的Pin1抑制活性。最有前途的化合物之一10a可以有效地抑制Pin1，其IC 50值为0.46μM，而它对GI 50值为1.82μM的前列腺癌细胞PC-3表现出优异的抗增殖作用。结构-活性关系表明，环A中合理的结构修饰对改善活性具有重要影响。进一步的机理研究表明10a降低了PC-3癌细胞中Cyclin D1的水平并导致细胞周期停滞在G0 / G1期。因此，化合物10a可以作为潜在的抗前列腺癌药物，通过抑制Pin1进行进一步研究。
• Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities
  作者：Bharani Meka、Suryachandra Rao Ravada、Muthyala Murali Krishna Kumar、Kurre Purna Nagasree、Trimurtulu Golakoti

  DOI：10.1016/j.bmc.2016.12.045

  日期：2017.2

  A new series of 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid analogs (5, 7, 8, 10, 13, 18a-d, 27a-c, 28a-d) were synthesized by modification of hydroxyl and acid functional moieties of boswellic acids. The structures of these analogs were confirmed by spectral data analysis (1H, 13C NMR and mass). Compounds 18b, 27a and 8 showed potent 5-lipoxygenase enzyme inhibitory activity (IC50:

  一系列新的11-酮-β-乳香酸和3-O-乙酰基-11-酮-β-乳香酸类似物（5、7、8、10、13、18a-d，27a-c，28a-d ）是通过修饰乳香酸的羟基和酸官能部分合成的。这些类似物的结构通过光谱数据分析（1 H，13 C NMR和质量）确认。化合物18b，27a和8显示出有效的5-脂氧合酶抑制活性（IC50：19.53、20.31和44.14μg/ mL）。计算研究表明，AKBA的选择性是由于它适合5-LOX受体，而其他酶（如12-LOX，COX-1和COX-2）则缺少该受体。我们的研究发现2-甲酰基和3-酮取代基对恢复在第4位具有必需COOH基团的非活性AKBA类似物的增强作用。
• Novel analogs of 3-o-acetyl-11-keto-ß-boswellic acid
  申请人：Gokaraju Raju Ganga

  公开号：US20060089409A1

  公开（公告）日：2006-04-27

  This invention relates to novel AKBA analogs of the formula I given below: Where in R 1 , R 2 , R 3 , R 4 and R 5 in each of the said analogs are:— 1. R 1 ═OCHO, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 2. R 1 ═OCOCH 2 Cl, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 3. R 1 =5′-O-methylgalloyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 4. R 1 ═OCOCH 2 CH 2 COOH, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 5. R 1 =8′,9′-Dihydro-4′-hydroxycinnamoyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 6. R 1 =4′-Hydroxycinnamoyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 7. R 1 =3′,4′-Dimethoxycinnamoyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 8. R 1 =3′,4′-Dihydroxy-5′-methoxycinnamoyloxy, R 2 ═H, R 3 COOH, R 4 & R 5 ═O 9. R 1 ═OCOCH 2 NH(tert-BOC), R 2 ═H, R 3 ═COOCH 3 , R 4 & R 5 ═O 10. R 1 ═OCOCH 2 NH 2 HCl, R 2 ═H, R 3 —COOH, R 4 & R 5 ═O 11. R 1 ═OCOCH(CH 3 )NH 2 HCl, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 12. R 1 ═H, R 2 ═OH, R 3 ═COOCH 3 , R 4 & R 5 ═O 13. R 1 ═H, R 2 ═Br, R 3 COOCH 3 , R 4 & R 5 ═O 14. R 1 ═CN, R 2 ═H, R 3 ═COOCH 3 , R 4 & R 5 ═O 15. R 1 ═SH, R 2 ═H, R 3 ═COOCH 3 , R 4 & R 5 ═O 16. R 1 & R 2 ═N(OH), R 3 ═COOCH 3 , R 4 & R 5 ═O 17. R 1 & R 2 ═H & OCOCH 3 R 3 ═H, R 4 & R 5 ═O 18. R 1 ═OCOCH 3 , R 2 ═H R 3 ═COOCH 2 CH 2 N(CH 3 ) 2 , R 4 & R 5 ═O 19. R 1 ═OCOCH 3 , R 2 ═H R 3 ═CONH 2 , R 4 & R 5 ═O 20. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CONHNH 2 , R 4 & R 5 ═O 21. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CONHCH 2 CH 2 NH 2 , R 4 & R 5 ═O 22. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CONHCH 2 CH 2 OH, R 4 & R 5 ═O 23. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CON(CH 2 CH 2 ) 2 NH, R 4 & R 5 ═O 24. R 1 ═OCOCH 3 , R 2 ═H R 3 ═NCO, R 4 & R 5 ═O 25. R 1 ═OCOCH 3 , R 2 ═H R 3 ═NH 2 , R 4 & R 5 ═O 26. R 1 ═OCOCH 3 , R 2 ═H R 3 ═CN, R 4 & R 5 ═O 27. R 1 ═OH, R 2 ═H R 3 ═COOH, R 4 & R 5 ═OH & H These compounds exhibited 5 -Lipoxigenase inhibitory properties and these compounds may be used in pharmaceutical compositions for therapeutic applications against a variety of inflammations and hypersensitivity-based human diseases including asthma, arthritis, bowel diseases such as ulcerative colitis and circulatory disorders such as shock and ischaemia. These compounds also inhibited the growth of Brine Shrimp in cultures, which may be considered as a positive indication for cytotoxicity and antitumor activity.

  本发明涉及下式 I 的新型 AKBA 类似物： 其中 R 1 , R 2 , R 3 , R 4 和 R 5 在上述每种类似物中为 1.R 1 ═OCHO, R 2 H, R 3 ═COOH, R 4 & R 5 ═O 2.R 1 ═OCOCH 2 Cl, R 2 H, R 3 ═COOH, R 4 & R 5 ═O 3.R 1 =5′-O-甲基甲酰氧基，R 2 ═H，R 3 ═COOH，R 4 & R 5 ═O 4.R 1 ═OCOCH 2 CH 2 COOH, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 5.R 1 =8′,9′-二氢-4′-羟基肉桂酰氧基，R 2 ═H，R 3 ═COOH，R 4 & R 5 ═O 6.R 1 =4′-羟基肉桂酰氧基，R 2 ═H，R 3 ═COOH，R 4 & R 5 ═O 7.R 1 =3′,4′-二甲氧基肉桂酰氧基，R 2 ═H，R 3 ═COOH，R 4 & R 5 ═O 8.R 1 =3′,4′-二羟基-5′-甲氧基肉桂酰氧基，R 2 ═H，R 3 COOH，R 4 & R 5 ═O 9.R 1 OCOCH 2 NH(叔丁氧羰基)，R 2 H, R 3 ═COOCH 3 , R 4 & R 5 ═O 10.R 1 OCOCH 2 NH 2 HCl, R 2 ═H, R 3 -COOH、R 4 & R 5 ═O 11.R 1 OCOCH(CH 3 )NH 2 HCl, R 2 ═H，R 3 ═COOH, R 4 & R 5 ═O 12.R 1 ═H，R 2 ═OH, R 3 ═COOCH 3 , R 4 & R 5 ═O 13.R 1 ═H, R 2 ═Br，R 3 COOCH 3 , R 4 & R 5 ═O 14.R 1 ═CN，R 2 H, R 3 ═COOCH 3 , R 4 & R 5 ═O 15.R 1 ═SH，R 2 ═H, R 3 ═COOCH 3 , R 4 & R 5 ═O 16.R 1 & R 2 ═N（OH），R 3 ═COOCH 3 , R 4 & R 5 ═O 17.R 1 & R 2 ═H & OCOCH 3 R 3 ═H, R 4 & R 5 ═O 18.R 1 OCOCH 3 , R 2 ═H R 3 ═COOCH 2 CH 2 N(CH 3 ) 2 , R 4 & R 5 ═O 19.R 1 OCOCH 3 , R 2 ═H R 3 ═CONH 2 , R 4 & R 5 ═O 20.R 1 OCOCH 3 , R 2 H, R 3 ═CONHNH 2 , R 4 & R 5 ═O 21.R 1 OCOCH 3 , R 2 H, R 3 ═CONHCH 2 CH 2 NH 2 , R 4 & R 5 ═O 22.R 1 OCOCH 3 , R 2 H, R 3 ═CONHCH 2 CH 2 OH，R 4 & R 5 ═O 23.R 1 OCOCH 3 , R 2 H, R 3 ═CON(CH 2 CH 2 ) 2 NH, R 4 & R 5 ═O 24.R 1 OCOCH 3 , R 2 ═H R 3 ═NCO, R 4 & R 5 ═O 25.R 1 OCOCH 3 , R 2 ═H R 3 ═NH 2 , R 4 & R 5 ═O 26.R 1 OCOCH 3 , R 2 ═H R 3 ═CN，R 4 & R 5 ═O 27.R 1 ═OH, R 2 ═H R 3 ═COOH, R 4 & R 5 ═OH & H 这些化合物表现出 5 -脂氧化酶抑制特性，这些化合物可用于药物组合物，以治疗各种炎症和超敏性人类疾病，包括哮喘、关节炎、肠道疾病（如溃疡性结肠炎）以及循环系统疾病（如休克和缺血）。这些化合物还能抑制盐水虾在培养物中的生长，可视为细胞毒性和抗肿瘤活性的积极迹象。
• Acyl derivatives of boswellic acids as inhibitors of NF-κB and STATs
  作者：Ajay Kumar、Bhahwal A. Shah、Samar Singh、Abid Hamid、Shashank K. Singh、Vijay K. Sethi、Ajit K. Saxena、Jaswant Singh、Subhash C. Taneja

  DOI：10.1016/j.bmcl.2011.10.112

  日期：2012.1

  Boswellic acid acylates including their epimers were synthesized and screened against a panel of human cancer cell lines. They exhibited a range of cytotoxicity against various human cancer cell lines thereby leading to the development of a possible SAR. One of the identified lead compounds was found to be an inhibitor of the NF-kappa B and STAT proteins, warranting further investigations to be developed into a potential anticancer lead. (C) 2011 Elsevier Ltd. All rights reserved.
• Cytotoxic and apoptotic activities of novel amino analogues of boswellic acids
  作者：Bhahwal A. Shah、Ajay Kumar、Pankaj Gupta、Madhunika Sharma、Vijay K. Sethi、Ajit K. Saxena、Jaswant Singh、Ghulam N. Qazi、Subhash C. Taneja

  DOI：10.1016/j.bmcl.2007.10.011

  日期：2007.12

  4-Amino analogues prepared from beta-boswellic acid and 11-keto-beta-boswellic acid, wherein the carboxyl group in ursane nucleus was replaced by an amino function via Curtius reaction, displayed improved cytotoxicity than the parent molecules. The same molecules also exhibited apoptotic activity by inducing DNA fragmentation. (c) 2007 Elsevier Ltd. All rights reserved.