(2S,3S,4R)-3,4-dihydroxy-6-methoxy-3-methyl-7-methylidene-2-pentyl-2,4-dihydropyrano[2,3-c]pyrrol-5-one | 1608461-36-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: (2S,3S,4R)-3,4-dihydroxy-6-methoxy-3-methyl-7-methylidene-2-pentyl-2,4-dihydropyrano[2,3-c]pyrrol-5-one
• CAS: 1608461-36-4
• 化学式: C₁₅H₂₃NO₅
• 分子量: 297.351
• InChiKey: PQXBZFLVJGBOAD-PSOPSSQASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  79.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2S,3R,4S)-3-hydroxy-6-methoxy-3-methyl-7-methylene-5-oxo-2-pentyl-2,3,4,5,6,7-hexahydropyrano[3,2c]pyrrol-4-ylmethanesulfonate 在 sodium acetate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 12.0h， 以80%的产率得到(2S,3S,4R)-3,4-dihydroxy-6-methoxy-3-methyl-7-methylidene-2-pentyl-2,4-dihydropyrano[2,3-c]pyrrol-5-one
  参考文献：
  名称：

  Synthetic and Biological Studies of Phaeosphaerides

  摘要：

  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.

  DOI：

  10.1021/jo500545d

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.