methyl grandiflorenate | 36100-66-0

• 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 grandiflorenate
• 英文别名: methyl ent-kaur-9(11)-16-dien-19-oate；(-)-4α-kaura-9(11),16-dien-19-oic acid methyl ester；grandiflorenic acid methyl ester；methyl (1S,4S,5R,9R,13R)-5,9-dimethyl-14-methylidenetetracyclo[11.2.1.01,10.04,9]hexadec-10-ene-5-carboxylate
• CAS: 36100-66-0
• 化学式: C₂₁H₃₀O₂
• 分子量: 314.468
• InChiKey: IXYPSKCWQCQDJQ-CULFCCOHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl grandiflorenate 在 四氧化锇 、 水 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 叔丁醇 为溶剂， 以89%的产率得到methyl-16α,17-dihydroxy-16,17-dihydro-9(11)-dehydro-ent-kaurenoate
  参考文献：
  名称：

  Synthesis and induction of apoptosis signaling pathway of ent-kaurane derivatives

  摘要：

  Thirty one ent-kaurane derivatives were prepared from kaurenoic acid (1), grandiflorenic acid (16), 15 alpha-acetoxykaurenoic acid (26) and 16 alpha-hydroxy-kaurenoic acid (31). They were tested for their ability to inhibit cell viability in the mouse leukemic macrophagic RAW 264.7 cell line. The most effective compounds were 12, 20, 21, and 23. These were selected for further evaluation in other human cancer cell lines such as Hela, HepG2, and HT-29. Similar effects were obtained although RAW 264.7 cells were more sensitive. In addition, these compounds were significantly less cytotoxic in non-transformed cells. The apoptotic potential of the most active compounds was investigated and they were able to induce apoptosis with compound 12 being the best inducer. The caspase-3, -8 and -9 activities were measured. The results obtained showed that compounds 12, 21, and 23 induce apoptosis via the activation of caspase-8, whereas compound 20 induces apoptosis via caspase-9. Immunoblot analysis of the expression of p53, Bax, Bcl-2, Bcl-xl, and IAPs in RAW 264.7 cells was also carried out. When cells were exposed to 5 mu M of the different compounds, expression levels of p53 and Bax increased whereas levels of antiapoptotic proteins such as Bc1-2, Bc1-x1, and IAPs decreased. In conclusion, kaurane derivatives (12, 20, 21, and 23) induce apoptosis via both the mitochondrial and membrane death receptor pathways, involving the Bcl-2 family proteins. Taken together these results provide a role of kaurane derivatives as apoptotic inducers in tumor cells. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.11.064
• 作为产物：
  描述：

  stenolobin 在 吡啶 、 氯化亚砜 作用下， 以90%的产率得到methyl grandiflorenate
  参考文献：
  名称：

  ENT-KAURENOID METHYL ESTERS FROMViguiera stenoloba, STRUCTURAL REVISION OF STENOLOBIN AND ITS BIOMIMETIC CONVERSION TO ZOAPATLIN

  摘要：

  从 Viguira stenoloba 中分离出的一种二萜--stenolobin 的结构被修订为 5。新的二萜 15α-angeloyloxy stenolobin 也是从同一植物中分离出来的。文中描述了将石蒜甙（5）转化为zoapatlin的生物仿生过程。

  DOI：

  10.1246/cl.1984.1237

文献信息

• X-ray Crystal Structure of Grandiflorenic Acid [(−)-kaura-9(11)-16-dien-19-oic Acid] Methyl Ester, a Compound Formerly Considered as an Oily Derivative
  作者：Perla Cruz-Mondragón、M. Concepción Lozada、Benjamín Ortiz、Raúl G. Enríquez、Manuel Soriano-García

  DOI：10.1007/s10870-008-9507-7

  日期：2009.7

  P21, lattice constants: a = 7.2170(10), b = 11.4170(10), c = 11.2850(10) Å, β = 98.700(10)°, V = 919.1(2) Å3 and Z = 2.Index AbstractGrandiflorenic acid [(−)-kaura-9(11)-16-dien-19-oic acid] methyl ester (2) was synthesized. This compound was formerly considered as an oily derivative. The crystal structure of (2) was obtained by determination of X-ray diffraction from suitable single crystals.

  Grandiflorenic acid [(-)-kaura-9(11​​)-16-dien-19-oic acid] 甲酯 (2), C21H30O2，是从 Grandiflorenic acid 合成的，从植物 Montanoa tomentosa 中分离出来。化合物(2)以前被描述为油性衍生物。(2) 的 X 射线衍射分析表明它由四个环、三个六元环 (I、II 和 III) 和一个五元环 (IV) 组成。I、II 和 III 环分别出现在椅子、扭曲和信封构象中。环 IV 出现在信封和半椅之间的构象中。大花烯酸甲酯晶体为单斜晶系，空间群为P21，晶格常数：a = 7.2170(10), b = 11.4170(10), c = 11.2850(10) Å, β = 98.700(10)°, V = 919.1(2) Å3 和 Z = 2。索引摘要合成了花序酸[(-)-kaura-9(1
• Synthesis and anti-inflammatory activity of ent-kaurene derivatives
  作者：Idaira Hueso-Falcón、Irene Cuadrado、Florencia Cidre、Juan M. Amaro-Luis、Ángel G. Ravelo、Ana Estevez-Braun、Beatriz de las Heras、Sonsoles Hortelano

  DOI：10.1016/j.ejmech.2011.01.052

  日期：2011.4

  inhibition of NF-κB activation might be the mechanism involved in anti-inflammatory effects of these kaurene derivatives. As expected, cytokines IL-6, IL-1α, TNF-α and IFN-γ were downregulated in the presence of compound 28, 55 and 62 after stimulation with LPS. These results indicate that kaurene derivatives might be used for the design of new anti-inflammatory agents.

  制备了一系列的贝壳杉烯衍生物（1 – 63），并评估了其抗炎活性。13种测试化合物能够抑制NO的产生，IC 50为2至10μM。化合物11，12，14和23显示细胞存活力的低百分比，而化合物9，10，17，28，37，48，55，61和62在浓度高达25μM时无细胞毒性。概述了一些结构-活动关系。化合物28，55和62，选择作为代表性的化合物，它们有效地抑制NOS-2蛋白的表达。我们还确定抑制NF-κB活化可能是这些贝壳杉烯衍生物的抗炎作用所涉及的机制。如所预期的，细胞因子IL-6，IL-1α，TNF-α和IFN-γ水平在化合物存在下调28，55和62用LPS刺激后。这些结果表明，kaurene衍生物可用于设计新的抗炎药。
• Structure of Grandiflorenic Acid
  作者：F. Piozzi、S. Passannanti、M. L. Marino、V. Sprio

  DOI：10.1139/v72-016

  日期：1972.1.1

  Grandiflorenic acid is determined to be structure 2, (−)-kaura-9(11),16-dien-19-oic acid.

  Grandiflorenic酸的结构被确定为结构2，(−)-kaura-9(11),16-dien-19-oic酸。
• Bioinspired Synthesis of Platensimycin from Natural <i>ent</i>-Kaurenoic Acids
  作者：Álvaro Pérez、José F. Quílez del Moral、Alberto Galisteo、Juan M. Amaro、Alejandro F. Barrero

  DOI：10.1021/acs.orglett.3c01470

  日期：2023.7.28

  The biomimetic formal synthesis of the antibiotic platensimycin for the treatment of infection by multidrug-resistant bacteria was accomplished starting from either ent-kaurenoic acid or grandiflorenic acid, each of which is a natural compound available in multigram scale from its natural source. Apart from the natural origin of the selected precursors, the keys of the described approach are the long-distance

  用于治疗多重耐药细菌感染的抗生素平板霉素的仿生正式合成是从对映贝壳杉烯酸或大花烯酸开始完成的，这两种酸都是来自其天然来源的多克规模的天然化合物。除了所选前体的天然来源外，所述方法的关键是对映贝壳杉烯酸在 C11处的长距离官能化以及二萜框架 A 环降解的有效方案。
• Synthesis, cytotoxicity and antiplasmodial activity of novel ent -kaurane derivatives
  作者：Ronan Batista、Pablo A. García、María Angeles Castro、José M. Miguel del Corral、Nivaldo L. Speziali、Fernando de P. Varotti、Renata C. de Paula、Luis F. García-Fernández、Andrés Francesch、Arturo San Feliciano、Alaíde B. de Oliveira

  DOI：10.1016/j.ejmech.2012.12.010

  日期：2013.4

  This paper reports on the syntheses and spectrometric characterisation of eleven novel ent-kaurane diterpenoids, including a complete set of H-1, C-13 NMR and crystallographic data for two novel ent-kaurane diepoxides. Moreover, the antineoplastic cytotoxicity for kaurenoic acid and the majority of ent-kaurane derivatives were assessed in vitro against a panel of fourteen cancer cell lines, of which allylic alcohols were shown to be the most active compounds. The good in vitro antimalarial activity and the higher selectivity index values observed for some ent-kaurane epoxides against the chloroquine-resistant W2 clone of Plasmodium falciparum indicate that this class of natural products may provide new hits for the development of antimalarial drugs. (C) 2013 Elsevier Masson SAS. All rights reserved.