methyl 8-acetyl-6-hydroxy-5-oxo-1,2,3-trihydroindolizine-3-carboxylate | 229640-38-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 8-acetyl-6-hydroxy-5-oxo-1,2,3-trihydroindolizine-3-carboxylate
• 英文别名: methyl (3S)-8-acetyl-6-hydroxy-5-oxo-2,3-dihydro-1H-indolizine-3-carboxylate
• CAS: 229640-38-4
• 化学式: C₁₂H₁₃NO₅
• 分子量: 251.239
• InChiKey: OLVMQKTUHPVKQE-VIFPVBQESA-N

物化性质

• 沸点：
  466.6±45.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 8-acetyl-6-hydroxy-5-oxo-1,2,3-trihydroindolizine-3-carboxylate 在 bis-triphenylphosphine-palladium(II) chloride 、 palladium on activated charcoal 氢气 、 双氧水 、 三乙胺 、 三氟乙酸 作用下， 以 氯仿 、 乙腈 为溶剂， 生成 methyl 3-(8-acetyloxy-3-(methoxycarbonyl)-5-oxo-1,2,3-trihydroindolizin-6-yl)propanoate
  参考文献：
  名称：

  Synthesis of the Angiotensin Converting Enzyme Inhibitor (−)-A58365A via an Cycloaddition Reaction

  摘要：

  The angiotensin converting enzyme inhibitor (-)-A58365A (1) was synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl substituted isomunchnone intermediate. The starting material for this process was prepared from L-pyroglutamic acid and involved using a diazo-phenylsulfonyl substituted pyrrolidine imide. Treatment of the diazoimide with Rh-2(OAc)(4) in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative which was subsequently converted to the ACE inhibitor in six additional steps.

  DOI：

  10.1021/ol9905497
• 作为产物：
  描述：

  L-焦谷氨酸 在 rhodium(II) acetate dimer 、 Oxone 、 Dowex 50WX₂-200 、 4-乙酰氨基苯磺酰叠氮 、 三乙胺 作用下， 以 甲醇 、 乙腈 、 苯 为溶剂， 反应 72.0h， 生成 methyl 8-acetyl-6-hydroxy-5-oxo-1,2,3-trihydroindolizine-3-carboxylate
  参考文献：
  名称：

  An Isomünchnone-Based Method for the Synthesis of Highly Substituted 2(1H)-Pyridones

  摘要：

  1-(Benzenesulfonyl-diazoacetyl)-pyrrolidin-2-one was prepared by a diazo transfer of 1-(benzenesulfonylacetyl)-pyrrolidin-2-one with p-acetamidobenzenesulfonyl azide and triethylamine. Treatment; of the diazoimide with a catalytic quantity of rhodium(II) acetate resulted in the formation of an isomunchnone dipole, which underwent bimolecular trapping with various dipolarophiles in high yield. The initially formed cycloadducts were not isolable or observed, as they all readily underwent ring opening to give the 3-hydroxy-2(1H)-pyridone ring system. The 3-hydroxy-2(1H)-pyridones were readily converted to the corresponding triflates, which function as suitable substrates in various types of palladium-catalyzed cross-coupling reactions. Commercial tetrakis(triphenylphoshine)palladium was found to be a particularly effective catalyst for the cross-coupling with aryl, vinyl, and acetylenic partners. An application of the method to the synthesis of the indolizidine alkaloid (+/-)-ipalbidine was carried out in eight steps in 17% overall yield. The angiotensin-converting enzyme inhibitor (-)-A58365A was also synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl substituted isomunchnone intermediate. The starting material for this process was prepared from L-pyroglutamic acid and involved using a diazo phenylsulfonyl substituted pyrrolidine imide. Treatment of the diazoimide with Rh-2(OAc)(4) in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative, which was subsequently converted to the ACE inhibitor in six additional steps.

  DOI：

  10.1021/jo9911600

文献信息

• Pyrrolidinyl pyridone and pyrazinone analogues as potent inhibitors of prolyl oligopeptidase (POP)
  作者：Curt D. Haffner、Caroline J. Diaz、Aaron B. Miller、Robert A. Reid、Kevin P. Madauss、Annie Hassell、Mary H. Hanlon、David J.T. Porter、J. David Becherer、Luke H. Carter

  DOI：10.1016/j.bmcl.2008.06.067

  日期：2008.8

  We report the synthesis and in vitro activity of a series of novel pyrrolidinyl pyridones and pyrazinones as potent inhibitors of prolyl oligopeptidase (POP). Within this series, compound 39 was co-crystallized within the catalytic site of a human chimeric POP protein which provided a more detailed understanding of how these inhibitors interacted with the key residues within the catalytic pocket.
• An Isomünchnone-Based Method for the Synthesis of Highly Substituted 2(1<i>H</i>)-Pyridones
  作者：Albert Padwa、Scott M. Sheehan、Christopher S. Straub

  DOI：10.1021/jo9911600

  日期：1999.11.1

  1-(Benzenesulfonyl-diazoacetyl)-pyrrolidin-2-one was prepared by a diazo transfer of 1-(benzenesulfonylacetyl)-pyrrolidin-2-one with p-acetamidobenzenesulfonyl azide and triethylamine. Treatment; of the diazoimide with a catalytic quantity of rhodium(II) acetate resulted in the formation of an isomunchnone dipole, which underwent bimolecular trapping with various dipolarophiles in high yield. The initially formed cycloadducts were not isolable or observed, as they all readily underwent ring opening to give the 3-hydroxy-2(1H)-pyridone ring system. The 3-hydroxy-2(1H)-pyridones were readily converted to the corresponding triflates, which function as suitable substrates in various types of palladium-catalyzed cross-coupling reactions. Commercial tetrakis(triphenylphoshine)palladium was found to be a particularly effective catalyst for the cross-coupling with aryl, vinyl, and acetylenic partners. An application of the method to the synthesis of the indolizidine alkaloid (+/-)-ipalbidine was carried out in eight steps in 17% overall yield. The angiotensin-converting enzyme inhibitor (-)-A58365A was also synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl substituted isomunchnone intermediate. The starting material for this process was prepared from L-pyroglutamic acid and involved using a diazo phenylsulfonyl substituted pyrrolidine imide. Treatment of the diazoimide with Rh-2(OAc)(4) in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative, which was subsequently converted to the ACE inhibitor in six additional steps.
• Synthesis of the Angiotensin Converting Enzyme Inhibitor (−)-A58365A via an Cycloaddition Reaction
  作者：Christopher S. Straub、Albert Padwa

  DOI：10.1021/ol9905497

  日期：1999.7.1

  The angiotensin converting enzyme inhibitor (-)-A58365A (1) was synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl substituted isomunchnone intermediate. The starting material for this process was prepared from L-pyroglutamic acid and involved using a diazo-phenylsulfonyl substituted pyrrolidine imide. Treatment of the diazoimide with Rh-2(OAc)(4) in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative which was subsequently converted to the ACE inhibitor in six additional steps.