5-(2-methylene-5,5,8a-trimethyl-(1R,4aR,8aR)-decahydronaphthalen-1-yl)-3-methylpent-2E-enoic acid | 20257-75-4

• 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: 5-(2-methylene-5,5,8a-trimethyl-(1R,4aR,8aR)-decahydronaphthalen-1-yl)-3-methylpent-2E-enoic acid
• 英文别名: (-)-copalic acid；ent-copalic acid；copalic acid；(E)-5-[(1R,4aR,8aR)-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-3-methylpent-2-enoic acid
• CAS: 20257-75-4
• 化学式: C₂₀H₃₂O₂
• 分子量: 304.473
• InChiKey: JFQBNOIJWROZGE-HPMXROJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(2-methylene-5,5,8a-trimethyl-(1R,4aR,8aR)-decahydronaphthalen-1-yl)-3-methylpent-2E-enoic acid 在 lithium aluminium tetrahydride 、 甲酸 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 46.0h， 生成 (1S,4aS,4bR,8aR,10aS)-1-Hydroxymethyl-2,4b,8,8,10a-pentamethyl-tetradecahydro-phenanthren-3-ol
  参考文献：
  名称：

  The C-13 configuration of the bromine-containing diterpene isoaplysin-20. Synthesis of debromoisoaplysin-20 and C-13 epimer

  摘要：

  DOI：

  10.1021/jo01291a028
• 作为产物：
  描述：

  穿心莲内酯 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 potassium permanganate 、 偶氮二异丁腈 、 硫酸 、 potassium tert-butylate 、 三正丁基氢锡 、 乙酸酐 、 sodium hydride 、 magnesium sulfate 、 对甲苯磺酸 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 氯仿 、 水 、 二甲基亚砜 、 异丙醇 、 丙酮 、 甲苯 、 叔丁醇 为溶剂， 反应 66.01h， 生成 5-(2-methylene-5,5,8a-trimethyl-(1R,4aR,8aR)-decahydronaphthalen-1-yl)-3-methylpent-2E-enoic acid
  参考文献：
  名称：

  通过区域选择性的Barton-McCombie反应从穿心莲内酯合成（-）-鸟氨酸和（-）-铜酸

  摘要：

  描述了具有抗菌活性的对-拉丹二萜（-）-agathic酸（1）的首次合成。从容易获得且廉价的穿心莲内酯开始，采用具有14个步骤的线性序列的手性池方法。就Barton-McCombie自由基反应而言，区域选择性脱氧完成了合成中的关键步骤。（-）-椰油酸（2），（-）-agathic酸的类似物，已从关键中间体7分五步方便地合成。

  DOI：

  10.1016/j.tet.2015.12.022

文献信息

• Synthetic Studies on Natural Diterpenoid Glyceryl Esters
  作者：Nicon Ungur、Margherita Gavagnin、Angelo Fontana、Guido Cimino

  DOI：10.1016/s0040-4020(00)00097-1

  日期：2000.4

  Synthesis of natural bicyclic and tricyclic diterpenoid diacylglycerols has been performed by regioselective coupling of terpenoid acid with glycerol at 1′-sn position. This method may be considered a general approach to obtain optically active acylglycerols. The preparation of 13C-labelled geranylgeranoic acid glyceryl esters is also described here.

  天然双环和三环二萜类二酰基甘油的合成已通过萜类酸与甘油在1'- sn位置的区域选择性偶联而进行。该方法可以被认为是获得旋光酰基甘油的通用方法。这里还描述了13 C-标记的香叶基香叶酸甘油酯的制备。
• Copalic acid analogs down-regulate androgen receptor and inhibit small chaperone protein
  作者：Nethrie D. Idippily、Qiaoyun Zheng、Chunfang Gan、Aicha Quamine、Morgan M. Ashcraft、Bo Zhong、Bin Su

  DOI：10.1016/j.bmcl.2017.04.046

  日期：2017.6

  Copalic acid, one of the diterpenoid acids in copaiba oil, inhibited the chaperone function of α-crystallin and heat shock protein 27kD (HSP27). It also showed potent activity in decreasing an HSP27 client protein, androgen receptor (AR), which makes it useful in prostate cancer treatment or prevention. To develop potent drug candidates to decrease the AR level in prostate cancer cells, more copalic

  钴酸是copaiba油中的二萜酸之一，可抑制α-晶体蛋白和热激蛋白27kD（HSP27）的伴侣功能。它还显示出降低HSP27客户蛋白和雄激素受体（AR）的有效活性，使其可用于前列腺癌的治疗或预防。为了开发有效的候选药物来降低前列腺癌细胞中的AR水平，需要合成更多的椰油酸类似物。使用AR水平作为读数，筛选了15种椰油酸类似物，并且两种化合物的功效比椰油酸强得多。该化合物还剂量依赖性地抑制AR阳性前列腺癌细胞的生长。此外，它们也抑制α-结晶蛋白的伴侣活性。
• New Non-Toxic Semi-Synthetic Derivatives from Natural Diterpenes Displaying Anti-Tuberculosis Activity
  作者：Priscilla Matos、Brian Mahoney、Yohan Chan、David Day、Mirela Cabral、Carlos Martins、Raquel Santos、Jairo Bastos、Philip Page、Vladimir Heleno

  DOI：10.3390/molecules201018264

  日期：——

  We report herein the synthesis of six diterpene derivatives, three of which are new, generated through known organic chemistry reactions that allowed structural modification of the existing natural products kaurenoic acid (1) and copalic acid (2). The new compounds were fully characterized using high resolution mass spectrometry, infrared spectroscopy, 1H- and 13C-NMR experiments. We also report the evaluation of the anti-tuberculosis potential for all compounds, which showed some promising results for Micobacterium tuberculosis inhibition. Moreover, the toxicity for each of the most active compounds was also assessed.

  我们在此报告了六种二萜衍生物的合成，其中三种是新的，通过已知的有机化学反应产生，允许对现有天然产物贝壳杉烯酸 (1) 和柯巴酸 (2) 进行结构修饰。使用高分辨率质谱、红外光谱、1H 和 13C-NMR 实验对新化合物进行了全面表征。我们还报告了所有化合物的抗结核潜力的评估，这显示出抑制结核分枝杆菌的一些有希望的结果。此外，还评估了每种最活跃化合物的毒性。
• Antitubercular Activity Increase in Labdane Diterpenes from Copaifera Oleoresin through Structural Modification
  作者：Aline Silva、Ana Carolina Soares、Mirela Cabral、Alex de Andrade、Marilza da Silva、Carlos Martins、Rodrigo Veneziani、Sérgio Ambrósio、Jairo Bastos、Vladimir Heleno

  DOI：10.21577/0103-5053.20160268

  日期：——

  The labdane diterpenes copalic acid, 3 beta-acetoxy-copalic acid, 3 beta-hydroxy-copalic acid and ent-agathic acid were isolated from Copaifera langsdorffii oleoresin. These four compounds were submitted to structural modifications by reduction with hydrogen/palladium, esterification with diazomethane, esterification with methanol/sulfuric acid and conversion into sodium salt, furnishing 15 compounds. All compounds were assayed in vitro against Mycobacterium tuberculosis (H37Rv, ATCC 27294). The four compounds displayed minimum inhibitory concentration (MIC) value of 125 mu g mL(-1), and were not considered active. A methylated derivative of compound 3 beta-hydroxy-copalic acid, and a sodium salt of copalic acid displayed MIC values of 25 mu g mL(-1) (71.7 mu M) and 6.25 mu g mL(-1) (19.2 mu M), respectively. The sodium salt of copalic acid stood out by displaying similar activity in comparison with streptomycin (MIC 6.25 mu g mL(-1)) and a better activity compared to mu M value of pyrazinamide (MIC 3.12 mu g mL(-1); 25.34 mu M). Therefore, the methylated derivative of compound 3 beta-hydroxy-copalic acid and the sodium salt of copalic acid should be considered for further studies.
• (13<i>E</i>)-(−)-Labda-8(17),13-dien-15-oic Acid
  作者：R. Atencio、R. Gaitán、S. Pekerar、J. D. Medina

  DOI：10.1107/s0108270197003016

  日期：1997.8.15

  In the title compound, C20H32O2, the two six-membered rings have a C-1(4) chair conformation and the rings are trans-fused. The crystal structure is stabilized by approximately symmetric R-2(2)(8)-type hydrogen bonds.

表征谱图