(+/-)-methyl 7-<3-<(triethylsilyl)oxy>-5-oxo-1-cyclopenten-1-yl>-4(Z)-heptenoate | 78908-11-9

• 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: (+/-)-methyl 7-<3-<(triethylsilyl)oxy>-5-oxo-1-cyclopenten-1-yl>-4(Z)-heptenoate
• 英文别名: methyl 7-<5-oxo-3<(triethylsilyl)oxy>-1-cyclopenten-1-yl>-4(Z)-heptenoate；methyl 7-{5-oxo-3[(triethylsilyl)oxy]-1-cyclopenten-1-yl}-4(Z)-heptenoate；methyl (Z)-7-(5-oxo-3-triethylsilyloxycyclopenten-1-yl)hept-4-enoate
• CAS: 78908-11-9
• 化学式: C₁₉H₃₂O₄Si
• 分子量: 352.546
• InChiKey: AFROMGBOCHWMIL-HJWRWDBZSA-N

物化性质

• 沸点：
  406.1±45.0 °C(Predicted)
• 密度：
  1.00±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.57
• 重原子数：
  24.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (+/-)-methyl 7-<3-<(triethylsilyl)oxy>-5-oxo-1-cyclopenten-1-yl>-4(Z)-heptenoate 在 六甲基磷酰三胺 、 正丁基锂 、 N-环己基异丙基胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  米索前列醇的α链二烯衍生物的合成及其胃分泌特性。

  摘要：

  描述了米索前列醇的七种α链二烯衍生物在狗中的合成和胃中的抗分泌活性。这些化合物的制备中的关键中间体是C-9叔丁基二甲基甲硅烷基烯醇醚，它们是通过原位硅烷化衍生自α链不饱和环戊烯酮的铜酸酯烯酸酯获得的。这些中间体上的硒烯化反应提供了C2-C3反式二烯，在可能的情况下，也可进行共轭生成相应的C3-C4二烯。该系列中最有趣的结构是C5-C6顺式，C3-C4顺式/反式（1：1）二烯，无法色谱分离成单独的几何异构体。异构体混合物的胃抗分泌活性是通过胃内给药的米索前列醇的约3倍。

  DOI：

  10.1021/jm00157a013
• 作为产物：
  描述：

  methyl 8-(2-furanyl)-8-hydroxy-4(Z)-octenoate 在 咪唑 、 水 、 potassium carbonate 、 三氯乙醛 、 三乙胺 、 zinc(II) chloride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 38.5h， 生成 (+/-)-methyl 7-<3-<(triethylsilyl)oxy>-5-oxo-1-cyclopenten-1-yl>-4(Z)-heptenoate
  参考文献：
  名称：

  An efficient synthesis of the antisecretory prostaglandin enisoprost

  摘要：

  A 13-step synthesis of the antisecretory prostaglandin enisoprost was previously reported by Collins et al. 1 in 1983. The reported synthesis involved coupling of enone 6 with a cuprate reagent2 derived from a suitably substituted vinylstannane and cuprous pentyne to give enisoprost 10 in 60% yield after removal of protecting groups and chromatographic purification.Further development work on the synthesis of enisoprost has resulted in an improved method for preparing the key enone precursor 6 as outlined in Scheme I. Use of the trans-vinyl iodide 9 in place of the corresponding vinylstannane derivative and use of dilithiocyanocuprate3 coupling technology resulted in an 85% isolated yield of enisoprost 10 as outlined in Scheme II.Direct conversion of the terminal acetylene 8b into protected enisoprost via a one-pot process has also been accomplished as outlined in Scheme II. This latter modification greatly simplified the process and resulted in a 71% isolated yield of enisoprost 10.

  DOI：

  10.1021/jo00007a052

文献信息

• Chemistry and structure-activity relationships of C-17 unsaturated 18-cycloalkyl and cycloalkenyl analogs of enisoprost. Identification of a promising new antiulcer prostaglandin
  作者：P. W. Collins、A. F. Gasiecki、W. E. Perkins、G. W. Gullikson、R. G. Bianchi、S. W. Kramer、J. S. Ng、E. E. Yonan、L. Swenton

  DOI：10.1021/jm00172a017

  日期：1990.10

  cycloalkyl and cycloalkenyl analogues of enisoprost was synthesized to investigate the effects of omega chain unsaturation on gastric antisecretory activity and diarrheogenic side effects. Of these, the 17E, 18-cyclopentenyl analogue 5d displayed potent gastric antisecretory activity in dogs but very weak diarrheogenic properties in rats and is the most selective prostaglandin compound discovered in these

  合成了一系列的依诺前列素的δ17不饱和环烷基和环烯基类似物，以研究ω链不饱和度对胃抗分泌活性和腹泻副作用的影响。其中，17E，18-环戊烯基类似物5d在犬中显示出强效的胃分泌活性，但在大鼠中的腹泻作用非常弱，是在这些实验室中发现的最具选择性的前列腺素化合物。在结构上，5d在欧米茄链中同时包含共轭二烯和叔烯丙基醇，这些化学特征分别赋予一些有趣的氧化和酸催化差向异构化和烯丙基重排反应性。
• Synthesis and gastric antisecretory properties of 4,5 unsaturated derivatives of 15-deoxy-16-hydroxy-16-methylprostaglandin E1
  作者：Paul W. Collins、Esam Z. Dajani、Raphael Pappo、Alan F. Gasiecki、Robert G. Bianchi、Emmett M. Woods

  DOI：10.1021/jm00360a002

  日期：1983.6

  The synthesis and gastric antisecretory activities of the delta 4,5-cis, delta 4,5-trans, and 4,5-acetylenic analogues of 15-deoxy-16-hydroxy-16-methyl prostaglandin E1 methyl ester are described. The key step in the preparation of these compounds involved the stereospecific conjugate addition of a cuprate reagent to the appropriate cyclopentenones. Although the trans and acetylenic derivatives were

  描述了15-脱氧-16-羟基-16-甲基前列腺素E1甲酯的δ4，5-顺式，δ4，5-反式和4，5-炔属类似物的合成和胃抗分泌活性。制备这些化合物的关键步骤涉及向适当的环戊烯酮中立体定向共轭添加铜酸盐试剂。尽管反式和炔属衍生物是胃酸分泌的弱抑制剂，但顺式烯烃比饱和母体化合物更有效且作用时间更长。发现相对于母体16-羟基化合物和参考标准品（15S）-15-甲基-和16,16-二甲基前列腺素E2的选择性而言，相对于不需要的腹泻作用的选择性得到了改善。
• Synthesis and structure-activity relationships of acyclic .omega. chain conjugated diene analogs of enisoprost
  作者：P. W. Collins、R. L. Shone、W. E. Perkins、A. F. Gasiecki、V. J. Kalish、S. W. Kramer、R. G. Bianchi

  DOI：10.1021/jm00082a010

  日期：1992.2

  of acyclic omega chain conjugated diene analogues of enisoprost were synthesized and evaluated for gastric antisecretory and diarrheagenic activities in comparison to enisoprost and a previously identified cyclic dienyl analogue. Several novel approaches to the cuprate reagents involved in the synthesis of the series are described. From this SAR study, it appears that both the conjugated diene and

  合成了一系列依诺前列素的无环ω链共轭二烯类似物，并与依诺前列素和先前鉴定的环状二烯基类似物相比，评估了胃的抗分泌和腹泻活性。描述了用于合成该系列的铜酸盐试剂的几种新颖方法。从这项SAR研究中，似乎共轭二烯和欧米茄链的整体空间填充特性都是这些化合物的药理作用和选择性的重要组成部分，并且不需要环状结构。
• 18-Cycloalkyl analogs of enisoprost
  作者：Paul W. Collins、Alan F. Gasiecki、William E. Perkins、Gary W. Gullikson、Peter H. Jones、Raymond F. Bauer

  DOI：10.1021/jm00125a013

  日期：1989.5

  By use of standard cuprate methodology, a series of 18-cycloalkyl analogues of enisoprost was prepared in an effort to impede omega chain metabolism and prolong duration of gastric antisecretory activity. An initial product of omega chain oxidation, the C-20 hydroxy analogue, was also synthesized for pharmacological comparison. The cyclopropyl, cyclobutyl, and cyclopentyl analogues were approximately one-fourth as potent as enisoprost in inhibiting gastric acid secretion, while the cyclohexyl and cycloheptyl analogues showed very weak activity, and the 20-hydroxy compound was inactive at a dose 100 times the ED50 of enisoprost. The cyclobutyl compound had a longer duration of antisecretory action than enisoprost and the other cycloalkyl analogues. The cycloalkyl analogues unexpectedly possessed low diarrheogenic activity in rats.
• One-pot synthesis of protected prostaglandins from alkynes and cyclopentenones. In situ generation of higher order cyanocuprates derived from alkenylzirconium intermediates
  作者：Kevin A. Babiak、James R. Behling、John H. Dygos、Kathleen T. McLaughlin、John S. Ng、Vincent J. Kalish、Steven W. Kramer、Robert L. Shone

  DOI：10.1021/ja00176a080

  日期：1990.9