7-[(2R,3R)-3-(tert-Butyl-dimethyl-silanyloxy)-2-[(S)-3-(tert-butyl-dimethyl-silanyloxy)-octyl]-5-oxo-cyclopent-(E)-ylidene]-heptanoic acid methyl ester | 212069-99-3

• 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: 7-[(2R,3R)-3-(tert-Butyl-dimethyl-silanyloxy)-2-[(S)-3-(tert-butyl-dimethyl-silanyloxy)-octyl]-5-oxo-cyclopent-(E)-ylidene]-heptanoic acid methyl ester
• 英文别名: methyl (7E)-7-[(2R,3R)-3-[tert-butyl(dimethyl)silyl]oxy-2-[(3S)-3-[tert-butyl(dimethyl)silyl]oxyoctyl]-5-oxocyclopentylidene]heptanoate
• CAS: 212069-99-3
• 化学式: C₃₃H₆₄O₅Si₂
• 分子量: 597.039
• InChiKey: FQSMCQOUFWEIMP-PXQYZTMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.77
• 重原子数：
  40
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-[(2R,3R)-3-(tert-Butyl-dimethyl-silanyloxy)-2-[(S)-3-(tert-butyl-dimethyl-silanyloxy)-octyl]-5-oxo-cyclopent-(E)-ylidene]-heptanoic acid methyl ester 在 氢氟酸 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以94%的产率得到7-[(2R,3R)-3-Hydroxy-2-((S)-3-hydroxy-octyl)-5-oxo-cyclopent-(E)-ylidene]-heptanoic acid methyl ester
  参考文献：
  名称：

  Rational Design of Antitumor Prostaglandins with High Biological Stability

  摘要：

  Molecular design can overcome the metabolic instability of Delta(7)-PGA(1), while maintaining its antitumor potency. Saturation of the C(13)-C(14) double bond enhances the biological stability but decreases the antiproliferative activity. Configurational inversion of the isomerase-sensitive C(12) stereocenter from the natural S to the unnatural R geometry not only enhances biological stability but also significantly suppresses the growth of the tumor cells. The 12R derivatives markedly increase the induction of p21, a Cdk inhibitor, leading to sharp cell cycle arrest at the G(1) phase at a dose level so low that at this dose Delta(7)-PGA(1) methyl ester scarcely exerts an effect. These conspicuous biological properties lead to long-term suppression of tumor cell growth. The structure-stability relationship demonstrates that the stability of prostaglandins (PGs) is crucially controlled by the C(12) configuration and is unaffected by the geometry of the hydroxy-bearing C(15). The successful design of antitumor PGs resistant to enzymatic metabolism provides a new strategy applicable to creating a useful PG for cancer chemotherapy.

  DOI：

  10.1021/jm9801657
• 作为产物：
  描述：

  7-{(2R,3R)-3-(tert-Butyl-dimethyl-silanyloxy)-2-[(S)-3-(tert-butyl-dimethyl-silanyloxy)-octyl]-5-oxo-cyclopentyl}-7-hydroxy-heptanoic acid methyl ester 在 4-二甲氨基吡啶 、 甲基磺酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 21.0h， 以73%的产率得到7-[(2R,3R)-3-(tert-Butyl-dimethyl-silanyloxy)-2-[(S)-3-(tert-butyl-dimethyl-silanyloxy)-octyl]-5-oxo-cyclopent-(E)-ylidene]-heptanoic acid methyl ester
  参考文献：
  名称：

  Rational Design of Antitumor Prostaglandins with High Biological Stability

  摘要：

  Molecular design can overcome the metabolic instability of Delta(7)-PGA(1), while maintaining its antitumor potency. Saturation of the C(13)-C(14) double bond enhances the biological stability but decreases the antiproliferative activity. Configurational inversion of the isomerase-sensitive C(12) stereocenter from the natural S to the unnatural R geometry not only enhances biological stability but also significantly suppresses the growth of the tumor cells. The 12R derivatives markedly increase the induction of p21, a Cdk inhibitor, leading to sharp cell cycle arrest at the G(1) phase at a dose level so low that at this dose Delta(7)-PGA(1) methyl ester scarcely exerts an effect. These conspicuous biological properties lead to long-term suppression of tumor cell growth. The structure-stability relationship demonstrates that the stability of prostaglandins (PGs) is crucially controlled by the C(12) configuration and is unaffected by the geometry of the hydroxy-bearing C(15). The successful design of antitumor PGs resistant to enzymatic metabolism provides a new strategy applicable to creating a useful PG for cancer chemotherapy.

  DOI：

  10.1021/jm9801657