(2R,3S)-methyl 2,3-dihydroxy-2-methyloctanoate | 1403681-32-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2R,3S)-methyl 2,3-dihydroxy-2-methyloctanoate
• 英文别名: methyl (2R,3S)-2,3-dihydroxy-2-methyloctanoate
• CAS: 1403681-32-2
• 化学式: C₁₀H₂₀O₄
• 分子量: 204.266
• InChiKey: AAMSBYOTKLZTOC-WCBMZHEXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R,3S)-methyl 2,3-dihydroxy-2-methyloctanoate 在 氯磺酸 、 正丁基锂 、 三氧化硫吡啶 、 二异丁基氢化铝 、 三乙胺 、 二异丙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 2.68h， 生成 3-(hydroxy-2,2,4-(trimethyl-5-pentyl-1,3-dioxolan-4-yl)-methyl)-4-methoxy-5-methylenefuran-2(5H)-one
  参考文献：
  名称：

  Total Synthesis and Biological Activity of the Proposed Structure of Phaeosphaeride A

  摘要：

  The total synthesis of the structure assigned to the natural product phaeosphaeride A la was accomplished. The key steps involve the addition of vinyllithium reagent 7 to the acetonide-protected aldehyde 8 to access the carbon backbone of la, the introduction of the methoxylamino group followed by intramolecular hetero-Michael cyclization, and methanol elimination to form the dihydropyran ring. In this study, both enantiomers of la were synthesized and tested for biological activity. Preliminary results showed that (6R,7R,8R)-1a and (6S,7S,8S)-1a inhibit STAT3-dependent transcriptional activity in a dose-dependent manner and exhibit antiproliferative properties in breast (MDA-MB-231) and pancreatic (PANC-1) cancer cells.

  DOI：

  10.1021/jo301662e
• 作为产物：
  描述：

  正己醛 在 甲基磺酰胺 、 氢化奎宁 1,4-(2,3-二氮杂萘)二醚 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 反应 8.0h， 生成 (2R,3S)-methyl 2,3-dihydroxy-2-methyloctanoate
  参考文献：
  名称：

  Total Synthesis and Biological Activity of the Proposed Structure of Phaeosphaeride A

  摘要：

  The total synthesis of the structure assigned to the natural product phaeosphaeride A la was accomplished. The key steps involve the addition of vinyllithium reagent 7 to the acetonide-protected aldehyde 8 to access the carbon backbone of la, the introduction of the methoxylamino group followed by intramolecular hetero-Michael cyclization, and methanol elimination to form the dihydropyran ring. In this study, both enantiomers of la were synthesized and tested for biological activity. Preliminary results showed that (6R,7R,8R)-1a and (6S,7S,8S)-1a inhibit STAT3-dependent transcriptional activity in a dose-dependent manner and exhibit antiproliferative properties in breast (MDA-MB-231) and pancreatic (PANC-1) cancer cells.

  DOI：

  10.1021/jo301662e

文献信息

• Synthetic and Biological Studies of Phaeosphaerides
  作者：Anthoula Chatzimpaloglou、Mikhail Kolosov、T. Kris Eckols、David J. Tweardy、Vasiliki Sarli

  DOI：10.1021/jo500545d

  日期：2014.5.2

  The signal transducer and activator of transcription 3 (STAT3) has been validated as a suitable target for cancer therapy. Recent evidence by our group and others has shown that phaeosphaerides act as inhibitors of the STAT3 pathway. An efficient synthetic sequence to phaeosphaeride la has been previously disclosed. In this work, the first total synthesis of (+/-)-phaeosphaeride B (1d) and the unnatural phaeosphaeride 1b is reported. Additionally, the biological activities of la and 1b were investigated. (6S,7S,8S)-1a and (6R,7S,8S)-1b inhibited granulocyte colony-stimulating factor (GCSF)-stimulated phosphorylation of STAT1, STAT3, and STAT5 and IL-6-stimulated nuclear translocation of STAT3 alpha. In an SPR-based assay, (6S,7S,8S)-1a and (6R,7S,8S)-1b showed minimal ability to inhibit binding of STAT3 to its immobilized phosphotyrosylpeptide ligand (IC50 > 100 mu M). Thus, (6S,7S,8S)-1a and (6R,7S,8S)-1b are likely upstream inhibitors of a kinase in the STAT signaling pathway and do not act through the inhibition of STAT3 dimerization by the blocking of the SH2 binding domain.
• Total Synthesis and Biological Activity of the Proposed Structure of Phaeosphaeride A
  作者：Anthoula Chatzimpaloglou、Maria P. Yavropoulou、Karien E. Rooij、Ralf Biedermann、Uwe Mueller、Stefan Kaskel、Vasiliki Sarli

  DOI：10.1021/jo301662e

  日期：2012.11.2

  The total synthesis of the structure assigned to the natural product phaeosphaeride A la was accomplished. The key steps involve the addition of vinyllithium reagent 7 to the acetonide-protected aldehyde 8 to access the carbon backbone of la, the introduction of the methoxylamino group followed by intramolecular hetero-Michael cyclization, and methanol elimination to form the dihydropyran ring. In this study, both enantiomers of la were synthesized and tested for biological activity. Preliminary results showed that (6R,7R,8R)-1a and (6S,7S,8S)-1a inhibit STAT3-dependent transcriptional activity in a dose-dependent manner and exhibit antiproliferative properties in breast (MDA-MB-231) and pancreatic (PANC-1) cancer cells.