7-[(2R,3R)-2-((E)-(S)-3-Hydroxy-oct-1-enyl)-3-methylsulfanyl-5-oxo-cyclopent-(E)-ylidene]-heptanoic acid methyl ester | 188253-83-0

• 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: 7-[(2R,3R)-2-((E)-(S)-3-Hydroxy-oct-1-enyl)-3-methylsulfanyl-5-oxo-cyclopent-(E)-ylidene]-heptanoic acid methyl ester
• 英文别名: methyl (7E)-7-[(2R,3R)-2-[(E,3S)-3-hydroxyoct-1-enyl]-3-methylsulfanyl-5-oxocyclopentylidene]heptanoate
• CAS: 188253-83-0
• 化学式: C₂₂H₃₆O₄S
• 分子量: 396.591
• InChiKey: ZPIYBAXJDYXNOO-AINRBQIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.85
• 重原子数：
  27.0
• 可旋转键数：
  13.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  63.6
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  7-[(2R,3R)-2-((E)-(S)-3-Hydroxy-oct-1-enyl)-3-methylsulfanyl-5-oxo-cyclopent-(E)-ylidene]-heptanoic acid methyl ester 在 deuterio phosphate buffer 作用下， 以 氘代甲醇 为溶剂， 生成 甲硫醇 、 (7E,13E,15S)-9-氧代-15-羟基前列素-7,10,13-三烯-1-酸甲酯
  参考文献：
  名称：

  Chemical Implications for Antitumor and Antiviral Prostaglandins:  Reaction of Δ⁷-Prostaglandin A₁ and Prostaglandin A₁ Methyl Esters with Thiols

  摘要：

  Prostaglandins (PGs) such as Delta(12)-PGJ(2) and Delta(7)-PGA(1) methyl ester that possess a cross-conjugated dienone unit exhibit unique antitumor and antiviral activities independent of intracellular cAMP levels. These compounds are transported reversibly into cultured cells and accumulate in nuclei via covalent interaction, eliciting growth inhibition. PGA(1) methyl ester, a simple cyclopentenone analog, is less potent. The unique cellular behavior of the dienone PGs correlates well with their chemical properties. The PGs react specifically with thiol nucleophiles such as glutathione. Michael addition of thiols to Delta(7)-PGA(1) methyl ester, an alkylidenecyclopentenone derivative, occurs facilely at the endocyclic C(11) position rather than at the C(7) position. This process is reversible, and in solution phase, the adducts are in equilibrium with considerable amounts of free PG and thiols. However, the reaction of this PG with Sephatose-bound thiols, regarded to be plausible mimics of protein thiols, is irreversible, and the resulting adducts are dissociated only by alkali treatment. On the other hand, PGA(1) methyl ester reacts with soluble or polymer-anchored thiols at lower rates than Delta(7)-PGA(1) methyl ester, but the resulting thiol adducts are substantially more stable than those of the dienone PGs. This tendency of the PGA(1) methyl ester causes its equilibrium to shift to the adduct formation. The reversibility of the Michael reaction of PGs with thiols is consistent with their intracellular behavior and biological activities. Since glutathione adducts of PGs have no antiproliferative activities for cancer cells, the intracellular free PGs are presumed to interact with target molecules to cause cell growth inhibition. The involvement of the ATP-dependent glutathione S-conjugate export pump (GS-X pump) in the efflux of PGs is discussed. Thus, the marked difference in potency of the dienone and enone PGs is explained by considering the combined kinetic and thermodynamic properties and the action of the GS-X pump.

  DOI：

  10.1021/ja9628359
• 作为产物：
  描述：

  (7E,13E,15S)-9-氧代-15-羟基前列素-7,10,13-三烯-1-酸甲酯 、 sodium thiomethoxide 在 phosphate buffer 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 以33%的产率得到7-[(2R,3R)-2-((E)-(S)-3-Hydroxy-oct-1-enyl)-3-methylsulfanyl-5-oxo-cyclopent-(E)-ylidene]-heptanoic acid methyl ester
  参考文献：
  名称：

  Chemical Implications for Antitumor and Antiviral Prostaglandins:  Reaction of Δ⁷-Prostaglandin A₁ and Prostaglandin A₁ Methyl Esters with Thiols

  摘要：

  Prostaglandins (PGs) such as Delta(12)-PGJ(2) and Delta(7)-PGA(1) methyl ester that possess a cross-conjugated dienone unit exhibit unique antitumor and antiviral activities independent of intracellular cAMP levels. These compounds are transported reversibly into cultured cells and accumulate in nuclei via covalent interaction, eliciting growth inhibition. PGA(1) methyl ester, a simple cyclopentenone analog, is less potent. The unique cellular behavior of the dienone PGs correlates well with their chemical properties. The PGs react specifically with thiol nucleophiles such as glutathione. Michael addition of thiols to Delta(7)-PGA(1) methyl ester, an alkylidenecyclopentenone derivative, occurs facilely at the endocyclic C(11) position rather than at the C(7) position. This process is reversible, and in solution phase, the adducts are in equilibrium with considerable amounts of free PG and thiols. However, the reaction of this PG with Sephatose-bound thiols, regarded to be plausible mimics of protein thiols, is irreversible, and the resulting adducts are dissociated only by alkali treatment. On the other hand, PGA(1) methyl ester reacts with soluble or polymer-anchored thiols at lower rates than Delta(7)-PGA(1) methyl ester, but the resulting thiol adducts are substantially more stable than those of the dienone PGs. This tendency of the PGA(1) methyl ester causes its equilibrium to shift to the adduct formation. The reversibility of the Michael reaction of PGs with thiols is consistent with their intracellular behavior and biological activities. Since glutathione adducts of PGs have no antiproliferative activities for cancer cells, the intracellular free PGs are presumed to interact with target molecules to cause cell growth inhibition. The involvement of the ATP-dependent glutathione S-conjugate export pump (GS-X pump) in the efflux of PGs is discussed. Thus, the marked difference in potency of the dienone and enone PGs is explained by considering the combined kinetic and thermodynamic properties and the action of the GS-X pump.

  DOI：

  10.1021/ja9628359