(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenylocta-2,7-dienoic acid | 869195-52-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenylocta-2,7-dienoic acid
• CAS: 869195-52-8
• 化学式: C₁₅H₁₈O₃
• 分子量: 246.306
• InChiKey: ZBSVBXJMZITFMX-IIWDSHPISA-N

物化性质

• 沸点：
  468.5±45.0 °C(Predicted)
• 密度：
  1.140±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenylocta-2,7-dienoic acid 在 吡啶 、 2,4,6-三氯苯甲酰氯 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.5h， 生成 (3S,6R,7S,8S)-3,7-Bis-(tert-butyl-dimethyl-silanyloxy)-4,4,6,8-tetramethyl-9-((2E,7E)-(5S,6R)-6-methyl-8-phenyl-5-triethylsilanyloxy-octa-2,7-dienoyloxy)-5-oxo-nonanoic acid 2-trimethylsilanyl-ethyl ester
  参考文献：
  名称：

  Synthesis of Cryptothilone 1, the First Cryptophycin−Epothilone Hybrid

  摘要：

  A hybrid structure was synthesized in which one portion is characteristic of a cryptophycin and a second sector bears the signature of an epothilone. The hybrid, in contrast to parent cryptophycin and epothilone systems, showed no effect on the tubulin assembly reaction.

  DOI：

  10.1021/ol0614020
• 作为产物：
  描述：

  tert-butyl (2E,5S,6R,7E)-5-[(tert-butyldimethylsilyl)-oxy]-6-methyl-8-phenylocta-2,7-dienoate 在 三氟乙酸 、 甲苯 、 methanol-dichloromethane 作用下， 以 二氯甲烷 、 三氟乙酸 为溶剂， 反应 4.0h， 以Flash chromatography (2% MeOH/CH2Cl2+1% AcOH) afforded the title compound 9 (210 mg, 49%) as pale yellow oil的产率得到(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenylocta-2,7-dienoic acid
  参考文献：
  名称：

  MACROCYCLIZATION OF COMPOUNDS FROM SOLID SUPPORT USING THIOESTERASES

  摘要：

  本发明公开了一种使用固相支持化学和硫酯酶制备大环化合物的方法。同时还公开了新型大环化合物。

  公开号：

  US20090111152A1

文献信息

• Efficient, divergent synthesis of cryptophycin unit A analogues
  作者：Kyle L. Bolduc、Scott D. Larsen、David H. Sherman

  DOI：10.1039/c2cc32417b

  日期：——

  A flexible and divergent synthesis of cryptophycin unit A analogues is described. This method relies on iridium-catalysed stereo- and enantioselective crotylation and chemoselective one-pot oxidative olefination to access common intermediate . Heck, cross metathesis, and Suzuki-Miyaura reactions are illustrated for the generation of methyl ester unit A analogues .

  描述了一种灵活多变的隐藻素单元 A 类似物的合成方法。该方法依赖于铱催化的立体和对映选择性巴豆化和化学选择性一锅氧化烯化来获得常见的中间体。Heck、交叉复分解和 Suzuki-Miyaura 反应被说明用于生成甲酯单元 A 类似物。
• Chemoenzymatic Synthesis of Cryptophycin Anticancer Agents by an Ester Bond-Forming Non-ribosomal Peptide Synthetase Module
  作者：Yousong Ding、Christopher M. Rath、Kyle L. Bolduc、Kristina Håkansson、David H. Sherman

  DOI：10.1021/ja204716f

  日期：2011.9.21

  Cryptophycins (Crp) are a group of cyanobacterial depsipeptides with activity against drug-resistant tumors. Although they have been shown to be promising, further efforts are required to return these highly potent compounds to the clinic through a new generation of analogues with improved medicinal properties. Herein, we report a chemosynthetic route relying on the multifunctional enzyme CrpD-M2 that incorporates a 2-hydroxy acid moiety (unit D) into Cop analogues. CrpD-M2 is a unique non-ribosomal peptide synthetase (NRPS) module comprised of condensation-adenylation-ketoreduction-thiolation (C-A-KR-T) domains. We interrogated A-domain 2-keto and 2-hydroxy acid activation and loading, and KR domain activity in the presence of NADPH and NADH. The resulting 2-hydroxy acid was elongated with three synthetic Crp chain elongation intermediate analogues through ester bond formation catalyzed by CrpD-M2 C domain. Finally, the enzyme-bound seco-Crp products were macrolactonized by the Crp thioesterase. Analysis of these sequential steps was enabled through LC-FTICR-MS of enzyme-bound intermediates and products. This novel chemoenzymatic synthesis of Crp involves four sequential catalytic steps leading to the incorporation of a 2-hydroxy acid moiety in the final chain elongation intermediate. The presented work constitutes the first example where a NRPS-embedded KR domain is employed for assembly of a fully elaborated natural product, and serves as a proof-of-principle for chemoenzymatic synthesis of new Crp analogues.
• Enzymatic Release and Macrolactonization of Cryptophycins from a Safety-Catch Solid Support
  作者：Wolfgang Seufert、Zachary Q. Beck、David H. Sherman

  DOI：10.1002/anie.200703665

  日期：2007.12.10
• US8114640B2
  申请人：——

  公开号：US8114640B2

  公开（公告）日：2012-02-14
• [EN] MACROCYCLIZATION OF COMPOUNDS FROM SOLID SUPPORT USING THIOESTERASES<br/>[FR] MACROCYCLISATION DE COMPOSÉS À PARTIR D'UN SUPPORT SOLIDE À L'AIDE DE THIOESTÉRASES
  申请人：UNIV MICHIGAN OFFICE OF TECHNO

  公开号：WO2009059002A2

  公开（公告）日：2009-05-07

  A method of preparing macrocycles using solid support chemistry and thioesterases is disclosed. Also disclosed are novel macrocycles.