(7E,13E,15S)-9-氧代-15-羟基前列素-7,10,13-三烯-1-酸甲酯 | 92711-55-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: (7E,13E,15S)-9-氧代-15-羟基前列素-7,10,13-三烯-1-酸甲酯
• 英文名称: Δ⁷-prostaglandin A₁ methyl ester
• 英文别名: NEPP-1；methyl (7E)-7-[(2S)-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxocyclopent-3-en-1-ylidene]heptanoate
• CAS: 92711-55-2
• 化学式: C₂₁H₃₂O₄
• 分子量: 348.483
• InChiKey: IXHOCKABYZKXPB-KSEGEHKCSA-N

物化性质

• 沸点：
  484.3±45.0 °C(Predicted)
• 密度：
  1.107±0.06 g/cm3(Predicted)

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：

  (7E,13E,15S)-9-氧代-15-羟基前列素-7,10,13-三烯-1-酸甲酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以77%的产率得到
  参考文献：
  名称：

  Δ7-Prostaglandin C1: A primary metabolite of antitumor Δ7-prostaglandin A1 in the sera

  摘要：

  Delta(7)-PGA(1), an artificial antitumor prostaglandin, is metabolized rapidly in the rat serum to give Delta(7)-PGC(1) as a primary metabolite. This is further degradated to produce a complex mixture. The structure of Delta(7)-PGC(1) has been determined by comparison with a sample chemically synthesized by triethylamine treatment of Delta(7)-PGA(1). (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)10151-x
• 作为产物：
  描述：

  7-[(S)-2-[(E)-(S)-3-(tert-Butyl-dimethyl-silanyloxy)-oct-1-enyl]-5-oxo-cyclopent-3-en-(E)-ylidene]-heptanoic acid methyl ester 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 水 、 二甲基亚砜 为溶剂， 以80%的产率得到(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：

  Δ的合成7 -前列腺素阿1甲酯

  摘要：

  为了开发目标分子的合成，简要研究了在4-烯基环戊烯酮的α'位置的醛醇缩合反应。我们发现有效的反应条件（LDA在-78℃下在THF中）被施加到具有环戊烯酮的ω链和α链醛，得到之间的反应的抗和顺式在73分15％的收率醛醇，分别。甲羟烷基化的抗羟醛，然后消除甲磺酰氧基和C（15）的TBS氧基的甲硅烷基化提供了标题分子，它也是由顺式羟醛以高收率生产的。

  DOI：

  10.1016/s0040-4039(00)02329-7

文献信息

• A New Method for Installation of Aryl and Alkenyl Groups onto a Cyclopentene Ring and Synthesis of Prostaglandins
  作者：Yuichi Kobayashi、Modachur G. Murugesh、Miwa Nakano、Eisuke Takahisa、Shahid B. Usmani、Takayuki Ainai

  DOI：10.1021/jo020375y

  日期：2002.10.1

  establishing the generality of the reaction (Table 2, eqs 6 and 7). Starting with the products of the coupling reaction, syntheses of the prostaglandin intermediates 13 and 14 (for 11-deoxy-PGE(2) and PGA(2)) and Delta(7)-PGA(1) methyl ester (15) were accomplished efficiently. During these investigations, LDA, LiCA, and LHMDS were found to be equally efficient bases for aldol reaction at the alpha' (alpha prime)

  为了构建合成环戊烷的新策略，研究了过渡金属催化的顺式4-环戊烯-1,3-二醇单乙酸酯1与硬亲核试剂R（T）-m的偶联反应（图1中的等式1） 。尽管使用PhZnCl，PhSnMe（3），[Ph-B（Me）（OCH（Me）CH（Me）O）]-Li（+）（6a）（源自硼酸酯4a（R（T）= Ph）和MeLi）在钯或镍催化剂的存在下会导致产生未知化合物烯酮16和/或酮17或回收1，新的硼酸盐5a（由4a和n-BuLi衍生）在室温下在THF中存在镍催化剂（NiCl（2）（PPh（3））（2））提供了反式偶合产物2a（R（T）= Ph）和3a（R（T）= Ph）综合产量高，但产品比率低至0.9：1。比例提高到13：通过向反应混合物中加入t-BuCN和NaI，得到1。这是1与硬亲核试剂反应的第一个成功实例，用添加剂实现的比例增加是前所未有的。该试剂系统（硼酸盐5（1.2-1.8当量），NiCl（2）（P
• 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。
• Chemical Implications for Antitumor and Antiviral Prostaglandins:  Reaction of Δ⁷-Prostaglandin A₁ and Prostaglandin A₁ Methyl Esters with Thiols
  作者：Masaaki Suzuki、Makoto Mori、Terutake Niwa、Ryu Hirata、Kyoji Furuta、Toshihisa Ishikawa、Ryoji Noyori

  DOI：10.1021/ja9628359

  日期：1997.3.1

  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.