(2R,5S)-4,4'aalpha,5,5',6',7',8',8'a-八氢-2',5,5',5',8'abeta-五甲基螺[呋喃-2(3H),1'(4'H)-萘]-5-乙酸 | 1438-57-9

• 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
• 中文名称: (2R,5S)-4,4'aalpha,5,5',6',7',8',8'a-八氢-2',5,5',5',8'abeta-五甲基螺[呋喃-2(3H),1'(4'H)-萘]-5-乙酸
• 英文名称: grindelic acid
• 英文别名: Labd-7-en-15-oic acid, 9,13-epoxy-；2-[(2'S,4aS,8R,8aS)-2',4,4,7,8a-pentamethylspiro[2,3,4a,5-tetrahydro-1H-naphthalene-8,5'-oxolane]-2'-yl]acetic acid
• CAS: 1438-57-9
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: XLWWERNKTLITEF-MVJPYGJCSA-N

物化性质

• 熔点：
  100-101°
• 比旋光度：
  D -102.2°
• 沸点：
  434.7±28.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)
• LogP：
  5.650 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  (2R,5S)-4,4'aalpha,5,5',6',7',8',8'a-八氢-2',5,5',5',8'abeta-五甲基螺[呋喃-2(3H),1'(4'H)-萘]-5-乙酸 在 lithium aluminium tetrahydride 、 正丁基锂 、 copper(ll) sulfate pentahydrate 、 草酰氯 、 三苯基甲烷 、 sodium ascorbate 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 正庚烷 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 34.25h， 生成 1-(2-((1'R,4a'S,5S,8a'S)-2',5,5',5',8a'-pentamethyl-4,4a',5,5',6',7',8',8a'-octahydro-3H,4'H-spiro[furan-2,1'-naphthalene]-5-yl)ethyl)-4-(((1'R,4a'S,5S,8a'S)-2',5,5',5',8a'-pentamethyl-4,4a',5,5',6',7',8',8a'-octahydro-3H,4'H-spiro[furan-2,1'-naphthalene]-5-yl)methyl)-1H-1,2,3-triazole
  参考文献：
  名称：

  Derivatives of grindelic acid: From a non-active natural diterpene to synthetic antitumor derivatives

  摘要：

  Using several reactions that include homologations and asymmetric epoxidations as well as Ugi and Huisgen couplings, we generated a small focused library of new derivatives from the labdane-type diterpene grindelic acid. These compounds were evaluated as cytotoxic agents against a panel of five human solid tumor cell lines (HBL-100, HeLa, SW1573, T-47D, and WiDr). The presence of the diamide functionalizations enhanced the cytotoxic effect. N-Benzyl-N-(1-(benzylamino)-2-methyl-1-oxopropan-2-yl)grindelicamide, proved to be the most active product in all cell lines tested, with values of 0.95 (+/- 0.38) mu M against HBL-100 cells. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.06.013
• 作为产物：
  描述：

  methyl grindelate 在 氢氧化钾 作用下， 以 甲醇 、 水 为溶剂， 反应 48.0h， 生成 (2R,5S)-4,4'aalpha,5,5',6',7',8',8'a-八氢-2',5,5',5',8'abeta-五甲基螺[呋喃-2(3H),1'(4'H)-萘]-5-乙酸
  参考文献：
  名称：

  Stereocontrolled Synthesis of ent-Grindelic Acid. A Useful Example of Diastereofacial Guidance in an Oxonium Ion-Initiated Pinacolic Ring Expansion

  摘要：

  An enantioselective synthesis of (+)-grindelic acid is described, confirming that the dextrorotatory enantiomer is antipodal to the natural diterpenoid. The optically pure bicyclic ketone 5 representing the AB ring system is constructed from the levorotatory Wieland-Miescher ketone and must therefore possess the absolute configuration shown. Coupling of 5 with the 5-lithio derivative of optically active 2,3-dihydrofuran 3 derived from (R)-(-)-linalool was effected for the purpose of realizing acid-catalyzed rearrangement with generation of the appropriate spirocyclic framework. This key step is highly stereocontrolled, leading predominantly to 7. Once the advanced intermediate 15 is available in this fashion, its subsequent exposure to oxidation and dehydration steps led to the target molecule. The synthesis demonstrates unequivocally that natural (-)-grindelic acid is a true labdane diterpenoid.

  DOI：

  10.1021/jo960547p

文献信息

• Formation of grindelane dimers by microbial transformation
  作者：Joseph J. Hoffmann、Louis K .Hutter、Steven J. Dentali、Karl H. Schram、Neil E. Mackenzie

  DOI：10.1016/0031-9422(92)83444-4

  日期：1992.9

  Abstract The material balance for the biotransformation of grindelic acid by Aspergillus niger was determined along with the isolation of two novel dimers identified as methyl-8α-hydroxy-grindelate-7β- O -7′β-ether hydrate and methyl-3β-acetoxy-8α-hydroxy-grindelate-7β- O -7′β-ether hydrate. Also identified were the known 19-hydroxy-grindelic acid and the novel 6α,17-dihydroxy-grindelic acid. All compounds

  摘要 确定了黑曲霉生物转化甘地酸的物质平衡，并分离了两种新型二聚体，鉴定为甲基-8α-羟基-格林地酸-7β-O -7'β-醚水合物和甲基-3β-乙酰氧基- 8α-羟基-grindelate-7β-O -7'β-醚水合物。还确定了已知的 19-羟基-格林德酸和新的 6α,17-二羟基-格林德酸。所有化合物均以其乙酸甲酯衍生物的形式分离。已知的 3β-羟基-7α,8α-环氧格林德酸是将 3β-羟基-格林德酸用作生物转化底物时形成的唯一产物。
• COMPOUNDS AND COMPOSITIONS FOR TREATING INFECTION
  申请人：Chepkwony Paul Kiprono

  公开号：US20120190734A1

  公开（公告）日：2012-07-26

  Compounds from 14 Kenyan plants, including from the root of Dovyalis abyssinica and Clutia robusta have been characterized and isolated, and their uses are disclosed.

  来自14种肯尼亚植物的化合物已经被鉴定和分离，包括来自阿比西尼亚多维亚利斯和强健小簇花的根部，它们的用途已经被披露。
• Gonzalez-Sierra, Manuel; Olivieri, Alejandro C.; Colombo, Maria I., Journal of the Chemical Society. Perkin transactions I, 1989, p. 1393 - 1399
  作者：Gonzalez-Sierra, Manuel、Olivieri, Alejandro C.、Colombo, Maria I.、Ruveda, Edmundo A.

  DOI：——

  日期：——
• US8697660B2
  申请人：——

  公开号：US8697660B2

  公开（公告）日：2014-04-15
• Derivatives of grindelic acid: From a non-active natural diterpene to synthetic antitumor derivatives
  作者：Guillermo F. Reta、Alejandra I. Chiaramello、Celina García、Leticia G. León、Víctor S. Martín、José M. Padrón、Carlos E. Tonn、Osvaldo J. Donadel

  DOI：10.1016/j.ejmech.2013.06.013

  日期：2013.9

  Using several reactions that include homologations and asymmetric epoxidations as well as Ugi and Huisgen couplings, we generated a small focused library of new derivatives from the labdane-type diterpene grindelic acid. These compounds were evaluated as cytotoxic agents against a panel of five human solid tumor cell lines (HBL-100, HeLa, SW1573, T-47D, and WiDr). The presence of the diamide functionalizations enhanced the cytotoxic effect. N-Benzyl-N-(1-(benzylamino)-2-methyl-1-oxopropan-2-yl)grindelicamide, proved to be the most active product in all cell lines tested, with values of 0.95 (+/- 0.38) mu M against HBL-100 cells. (C) 2013 Elsevier Masson SAS. All rights reserved.