NEPP-3 | 92762-26-0

• 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: NEPP-3
• 英文别名: methyl (7E)-7-[(2R)-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxocyclopent-3-en-1-ylidene]heptanoate
• CAS: 92762-26-0
• 化学式: C₂₁H₃₂O₄
• 分子量: 348.483
• InChiKey: IXHOCKABYZKXPB-AEKKQFTFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  NEPP-3 以63%的产率得到7-[(R)-2-((E)-(S)-3-Hydroxy-oct-1-enyl)-5-oxo-cyclopent-3-en-(E)-ylidene]-heptanoic acid
  参考文献：
  名称：

  合成新的抗肿瘤前列腺素。

  摘要：

  通过三组份偶联过程，可以单锅进入受保护的 7-羟基-PGE1 衍生物，从而产生多种 C-7 功能化或不饱和的新 PG。这些烯酮和二烯酮衍生物在体外对 L1210 肿瘤细胞的生长具有很强的抑制活性。

  DOI：

  10.1248/cpb.32.4658
• 作为产物：
  描述：

  (1E,3S)-1-iodo-3-(tert-butyldimethylsiloxy)-1-octene 在 4-二甲氨基吡啶 、 Dimethylzinc 、 叔丁基锂 、 溶剂黄146 、 甲基磺酰氯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 31.0h， 生成 NEPP-3
  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

文献信息

• Synthesis of new antineoplastic prostaglandins.
  作者：Satoshi Sugiura、Takeshi Toru、Toshio Tanaka、Atsuo Hazato、Noriaki Okamura、Kiyoshi Bannai、Kenji Manabe、Seizi Kurozumi、Ryoji Noyori

  DOI：10.1248/cpb.32.4658

  日期：——

  The three-component coupling process allows a single-pot entry to protected 7-hydroxy-PGE1 derivatives, leading to a variety of new PGs functionalized or unsaturated at C-7. The enone and dienone derivatives exhibit potent inhibitory activity on L1210 tumor cell growth in vitro.

  通过三组份偶联过程，可以单锅进入受保护的 7-羟基-PGE1 衍生物，从而产生多种 C-7 功能化或不饱和的新 PG。这些烯酮和二烯酮衍生物在体外对 L1210 肿瘤细胞的生长具有很强的抑制活性。
• Rational Design of Antitumor Prostaglandins with High Biological Stability
  作者：Masaaki Suzuki、Toshihiro Kiho、Keiichiro Tomokiyo、Kyoji Furuta、Shoji Fukushima、Yoshikazu Takeuchi、Makoto Nakanishi、Ryoji Noyori

  DOI：10.1021/jm9801657

  日期：1998.7.1

  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.