15,16-epoxylabda-8(17),13,14-trien-18-oic acid | 1235-76-3

• 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: 15,16-epoxylabda-8(17),13,14-trien-18-oic acid
• 英文别名: lambertiainic acid；lambertianic acid；daniellic acid；16,17-Epoxy-labda-8(14),13(17),15-trien-19-saeure, Enantio-danielsaeure；Lambertiansaeure；Lambertiainc Acid；(1S,4aR,5S,8aR)-5-[2-(furan-3-yl)ethyl]-1,4a-dimethyl-6-methylidene-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carboxylic acid
• CAS: 1235-76-3；1235-77-4；4966-13-6；10267-14-8
• 化学式: C₂₀H₂₈O₃
• 分子量: 316.441
• InChiKey: ZQHJXKYYELWEOK-CUDHKJQZSA-N

物化性质

• 熔点：
  126-127 °C(Solv: methanol (67-56-1))
• 沸点：
  428.6±38.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)
• LogP：
  6.030 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  50.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  15,16-epoxylabda-8(17),13,14-trien-18-oic acid 在 palladium on activated charcoal 氢气 、 zinc trifluoromethanesulfonate 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 20.5h， 生成 (1RS,2SR,6RS,7RS)-8-[18-carboxy-13,14,15,16-tetranorlabd-8(17)-en-12-yl]-4,10-dioxatricyclo[5.2.1.0^2,6]decane-3,5-dione
  参考文献：
  名称：

  摘要：

  The Diels-Alder reaction of lambertianic acid with maleic anhydride occurred in a stereoselective fashion and yielded diastereoisomeric (1R,2S,6R,7R)- and (1S,2R,6S,7S)-exo-adducts. The latter reacted with L-valinol to give the corresponding diterpenoid imides, 4-aza-9-oxabicyclo[2.2.1]dec-8-enes. Reactions of lambertianic acid with N-substituted maleimides in the presence of Lewis acids afforded diastereoisomeric adducts having both exo and endo configuration. Some transformations of the adducts were examined with a view to obtain cantharidin and dihydroisoindole analogs.

  DOI：

  10.1023/a:1023490528591

文献信息

• Synthetic transformations of higher terpenoids. XXI.* Preparation of phlomisoic acid and its N-containing derivatives
  作者：M. E. Mironov、Yu. V. Kharitonov、E. E. Shul’ts、M. M. Shakirov、I. Yu. Bagryanskaya、G. A. Tolstikov

  DOI：10.1007/s10600-010-9577-6

  日期：2010.5

  A method for preparing 15,16-epoxylabda-8(9),13(16),14-trien-18-oic (phlomisoic) acid was proposed. Its structure was confirmed by an XSA. N-containing derivatives of phlomisoic acid that contained amines, hydrazides, and methyl esters of amino acids on the C-18 atom in addition to (2-oxo-2-aminoacetyl)-substituted derivatives of the C-16 methyl ester of phlomisoic acid were prepared.

  提出了一种制备15,16-环氧实验树脂-8(9),13(16),14-三烯-18-酸（克伦庚酸）的方法。其结构通过XSA得到确认。还制备了克伦庚酸的含氮衍生物，这些衍生物在C-18原子上含有胺、肼和氨基酸的甲基酯，此外还有克伦庚酸C-16甲基酯的(2-氧-2-氨基乙酰基)取代衍生物。
• Synthetic Transformations of Higher Terpenoids. 40. Synthesis and Assessment of Analgesic Activity of N-Containing Derivatives of Lambertianic Acid
  作者：Yu. V. Kharitonov、E. E. Shul’ts、T. V. Rybalova、A. V. Pavlova、T. G. Tolstikova

  DOI：10.1007/s10600-021-03502-y

  日期：2021.9

  New labdanoid derivatives containing hydrophilic substituents (amino, methylamino) in the C-4 position were synthesized via selective transformations of lambertianic acid chloride. A one-pot method was proposed to prepare 16-formyllambertianic acid amide and included selective formylation of lambertianic acid by POCl3 in DMF followed by amidation by aqueous NH4OH. The molecular structure of the compound

  通过朗伯坦酰氯的选择性转化，合成了在 C-4 位含有亲水性取代基（氨基、甲氨基）的新型劳丹脂衍生物。提出了一种一锅法来制备 16-甲酰基琥珀酸酰胺，包括在 DMF中通过 POCl 3对朗伯酸进行选择性甲酰化，然后通过 NH 4 OH水溶液进行酰胺化。通过X射线晶体结构分析研究了该化合物的分子结构。在化学刺激模型中发现了新合成的 4-amino-18-nor-15,16-epoxylabda-8(17),13,14-triene 和 4-(pyrrolidin-1-yl)-18-nor 的镇痛活性-15,16-epoxylabda-8(17),13,14-triene 草酸盐和 16-羟甲基)lambertianic 酰胺。
• An Approach toward 17-Arylsubstituted Marginatafuran-Type Isospongian Diterpenoids via a Palladium-Catalyzed Heck–Suzuki Cascade Reaction of 16-Bromolambertianic Acid
  作者：Yurii V. Kharitonov、Elvira E. Shults

  DOI：10.3390/molecules27092643

  日期：——

  palladium-catalyzed domino Heck–Suzuki reaction sequence for the synthesis of the tetracyclic skeleton of marginatafuran-type isospongian diterpenoids with a wide variety of substituents in the C-17 position is reported. The proposed approach was based on selective transformations of the accessible plant diterpenoid lambertianic acid and includes an intramolecular Heck reaction of 16-bromolambertianic and arylation

  异海绵二萜是从海洋生物（主要是海绵和海蛞蝓）中分离出来的一个小但不断增长的天然四环次级代谢产物家族。报道了钯催化的多米诺 Heck-Suzuki 反应序列，用于合成在 C-17 位具有多种取代基的边缘呋喃型异海绵二萜四环骨架。所提出的方法基于可获取的植物二萜类朗伯酸的选择性转化，包括 16-溴朗伯酸的分子内 Heck 反应和钯中间体与芳基硼酸的芳基化。研究了芳基硼酸和16-溴琥珀酸呋喃环中取代基的性质对反应方向和化学选择性的影响。
• Synthetic Transformations of Higher Terpenoids. 43. Synthesis and Cytotoxic Properties of New Lambertianic Acid Derivatives at the Carboxylic Group
  作者：Yu.V. Kharitonov、V. I. Antipova、M. K. Marenina、Yu.V. Meshkova、T. G. Tolstikova、E. E. Shults

  DOI：10.1007/s10600-023-04206-1

  日期：2023.11

  Lambertianic acid was selectively transformed at the carboxylic group. Synthetic methods for natural labdanoids, i.e., lambertianic acid methyl ester and lambertianol, were proposed. New N-containing diterpenoid derivatives with alkyl(aryl)amide, dialkylamide, hydrazide, N-hydroxycarbamoyl, and nitrile groups in the C-4 position of the labdane skeleton were synthesized via reactions of lambertianic

  朗伯酸在羧基处选择性地转化。提出了天然朗伯烷酸甲酯和朗伯酚的合成方法。通过朗伯田酰氯与脂肪族、芳香族胺、氨基酸的反应，合成了在拉丹烷骨架的C-4位上具有烷基（芳基）酰胺、二烷基酰胺、酰肼、N-羟基氨基甲酰基和腈基团的新型含氮二萜衍生物。 、肼和羟胺。获得了对 MCF-7、HeLa 和 HepG2（MTT 测定）人肿瘤细胞系具有比朗伯酸更高的细胞毒性的化合物。最活跃的朗伯酸N-羟基氨基甲酰衍生物的IC 50值为15μM（选择性指数>7）。
• Synthetic Transformations of Higher Terpenoids. 44#. Synthesis of New Derivatives of 18-Nor-4-Amino-8(17),13,14-Labdatriene and Evaluation of Their Cytotoxicity for MCF7, HepG2, and HeLa Tumor Cell Lines
  作者：Yu. V. Kharitonov、V. I. Antipova、M. K. Marenina、Yu. V. Meshkova、T. G. Tolstikova、E. E. Shults

  DOI：10.1007/s10600-024-04299-2

  日期：2024.3

  Various N-containing 18-norlabdanoids were synthesized via reactions of 18-nor-4-amino-15,16-epoxy-8(17),13(16),14-labdatriene with methyl iodide, aromatic aldehydes, acetic and trifluoroacetic acid anhydrides, benzoyl chloride, sulfonyl chlorides, bromoacetic acid chloride, and methyl bromoacetate and condensation with azidobenzoic acids. The cytotoxic activity (MTT assay) against MCF7, HepG2, and

  通过18-正-4-氨基-15,16-环氧-8(17),13(16),14-拉达三烯与碘甲烷、芳香醛、乙酸和三氟乙酸反应合成了多种含氮18-降拉布丹烷类化合物。酸酐、苯甲酰氯、磺酰氯、溴乙酰氯、溴乙酸甲酯以及与叠氮基苯甲酸的缩合。如果朗伯酸羧基被胺取代，则针对 MCF7、HepG2 和 HeLa 肿瘤细胞系的细胞毒活性（MTT 测定）显着增加。随后通过添加 N'-取代的甘氨酰胺部分对含 N 取代基进行修饰，改变了细胞毒性和选择性。合成的化合物对MCF7细胞系的活力影响最大。最活跃的化合物的IC 50值为8 μM。