grindelic acid | 170081-11-5

• 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: grindelic acid
• 英文别名: 2-[(2'R,4aR,8S,8aR)-2',4,4,7,8a-pentamethylspiro[2,3,4a,5-tetrahydro-1H-naphthalene-8,5'-oxolane]-2'-yl]acetic acid
• CAS: 170081-11-5
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: XLWWERNKTLITEF-XLNTUCKNSA-N

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

反应信息

• 作为反应物：
  描述：

  grindelic acid 在 溴 、 N-溴代乙酰胺 作用下， 以 甲醇 、 乙醚 、 水 、 丙酮 为溶剂， 反应 8.0h， 生成 methyl 2-((2R,3'S,4a'R,5R,8a'R)-3'-bromo-5,5',5',8a'-tetramethyl-2'-methylenedecahydro-2'H,3H-spiro[furan-2,1'-naphthalen]-5-yl)acetate
  参考文献：
  名称：

  Regio- and stereoselective hydroxylation of grindelic acid and its 3.ALPHA.-hydroxy derivative.

  摘要：

  通过分别给出的17-或7β-溴衍生物（6a，b或9a，b）在古二酸（1a）和3α-羟基古二酸（1b）的C-17或C-6位选择性地引入氢酰基通过与 Br2 或 NBA 溴化。 7β-羟基衍生物(17a,b)由8β-甲基-7-酮衍生物(14a,b)通过NaBH4还原得到。 7α-羟基衍生物(18a,b)是从在C-9位含有断裂结构的8,9-en-7-one衍生物(15a,b)选择性获得的。

  DOI：

  10.1248/cpb.39.2167
• 作为产物：
  描述：

  (2R,2'R,4'aR,5R,8'aR)-decahydro-2',5,5',5',8'a-pentamethyl-5-vinylspiro-2'-ol 在 吡啶 、 4-二甲氨基吡啶 、 氢氧化钾 、 sodium hydroxide 、 氯化亚砜 、 4 A molecular sieve 、 双氧水 、 碘 、 pyridinium chlorochromate 、 diborane(6) 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 68.0h， 生成 grindelic acid
  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

• Total synthesis of (+)-grindelic acid by stereocontrolled oxonium ion activated pinacol ring expansion. Chemical proof of the absolute configuration of all grindelane diterpenes
  作者：Leo A. Paquette、Hui-Ling Wang

  DOI：10.1016/0040-4039(95)01187-m

  日期：1995.8

  (+)-Grindelic acid, synthesized enantioselectively from the levorotatory Wieland-Miescher ketone and (-)-linalool and necessarily formulated as 1a, is shown to be antipodal to the major diterpenoid of Grindelia species.

  (+)-Grindelic酸是由左旋Wieland-Miescher酮和（-)-香叶醇对映选择性合成而得，并必须以1a的形式配制，研究表明其对映于Grindelia属主要的倍半萜。
• Hydroxygrindelane derivatives by microbial transformation
  作者：Joseph J. Hoffmann、Shivanand D. Jolad、Robert B. Bates、Fernando A. Camou

  DOI：10.1016/0031-9422(88)80109-2

  日期：1988.1

  Abstract The microbial transformation of methyl 7α,8α-epoxygrindelate and 6,8(17)-dehydrogrindelic acid by cultures of Aspergillus niger and Penicillium brevicompactum produced the corresponding 3α-hydroxygrindelanes.

  摘要 7α,8α-环氧格林地酸甲酯和6,8(17)-脱氢格林地酸甲酯通过黑曲霉和短缩青霉的微生物转化产生了相应的3α-羟基格林地烷。
• Stereocontrolled Synthesis of <i>ent</i>-Grindelic Acid. A Useful Example of Diastereofacial Guidance in an Oxonium Ion-Initiated Pinacolic Ring Expansion
  作者：Leo A. Paquette、Hui-Ling Wang

  DOI：10.1021/jo960547p

  日期：1996.1.1

  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.
• Regio- and stereoselective hydroxylation of grindelic acid and its 3.ALPHA.-hydroxy derivative.
  作者：Sayoko HIRANUMA、Takeshi SHIMIZU、Hirosuke YOSHIOKA

  DOI：10.1248/cpb.39.2167

  日期：——

  A hydrocyl group was selectively introduced at the C-17 or C-6 position of grindelic acid (1a) and 3α-hydroxygrindelic acid (1b) via the 17- or 7β-bromo derivatives (6a, b or 9a, b) given respectively by bromination with Br2 or NBA. The 7β-hydroxy derivatives (17a, b) were obtained via the 8β-methyl-7-one derivatives (14a, b) by reduction with NaBH4. The 7α-hydroxy derivatives (18a, b) were obtained selectively from the 8, 9-en-7-one derivatives (15a, b) which contain a cleaved structure at the C-9 position.

  通过分别给出的17-或7β-溴衍生物（6a，b或9a，b）在古二酸（1a）和3α-羟基古二酸（1b）的C-17或C-6位选择性地引入氢酰基通过与 Br2 或 NBA 溴化。 7β-羟基衍生物(17a,b)由8β-甲基-7-酮衍生物(14a,b)通过NaBH4还原得到。 7α-羟基衍生物(18a,b)是从在C-9位含有断裂结构的8,9-en-7-one衍生物(15a,b)选择性获得的。