(1R,5S)-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene-2-carboxylic acid | 172172-52-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (1R,5S)-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene-2-carboxylic acid
• 英文别名: (1R,5S)-2-carboxy-8-(tert-butoxycarbonyl)-8-azabicyclo<3.2.1>octene；(1R,5S)-8-(tert-Butoxycarbonyl)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid；(1R,5S)-8-[(2-methylpropan-2-yl)oxycarbonyl]-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid
• CAS: 172172-52-0
• 化学式: C₁₃H₁₉NO₄
• 分子量: 253.298
• InChiKey: WONKOBXMPJFGDL-PSASIEDQSA-N

物化性质

• 沸点：
  389.7±42.0 °C(Predicted)
• 密度：
  1.237±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,5S)-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene-2-carboxylic acid 在 甲基锂 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 5.92h， 生成 (1R,5S)-2-acetyl-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene
  参考文献：
  名称：

  Enantiospecific Synthesis of (+)- and (−)-Ferruginine from l-Glutamic Acid. Synthesis of Tropanes via Intramolecular Iminium Ion Cyclization

  摘要：

  Iminium ions, generated by decarbonylation of N-benzyl-5-[1-(methoxycarbonyl)-4-oxopentyl]-prolines, prolines, undergo intramolecular cyclization to afford 2,4-disubstituted tropanes in good yields. This transformation is also shown to be a stereospecific reaction. The value of these substituted tropanes has been demonstrated by functional group manipulation, leading to the enantiospecific synthesis of (+)-ferruginine, an alkaloid isolated from Darlinga ferruginea, and its unnatural enantiomer, (-)-ferruginine.

  DOI：

  10.1021/jo9515081
• 作为产物：
  描述：

  methyl (1R,5S)-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene-2-carboxylate 在 氢氧化钾 作用下， 以 异丙醇 为溶剂， 生成 (1R,5S)-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene-2-carboxylic acid
  参考文献：
  名称：

  Enantiospecific Synthesis of (+)- and (−)-Ferruginine from l-Glutamic Acid. Synthesis of Tropanes via Intramolecular Iminium Ion Cyclization

  摘要：

  Iminium ions, generated by decarbonylation of N-benzyl-5-[1-(methoxycarbonyl)-4-oxopentyl]-prolines, prolines, undergo intramolecular cyclization to afford 2,4-disubstituted tropanes in good yields. This transformation is also shown to be a stereospecific reaction. The value of these substituted tropanes has been demonstrated by functional group manipulation, leading to the enantiospecific synthesis of (+)-ferruginine, an alkaloid isolated from Darlinga ferruginea, and its unnatural enantiomer, (-)-ferruginine.

  DOI：

  10.1021/jo9515081

文献信息

• Process for producing optically active tropinonemonocarboxylic acid ester derivative
  申请人：NIHON MEDI-PHYSICS CO., LTD.

  公开号：US20030065183A1

  公开（公告）日：2003-04-03

  An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol %, and its optical purity was 70 to 97% ee. In addition, it was found that a crystalline optically active anhydroecgonine carboxylic acid ester derivative can be obtained by reducing and then dehydrating the optically active tropinonemonocarboxylic acid ester derivative and that its optical purity can easily be increased by recrystallization.

  通过将琥珀二醛与有机胺和乙酰二羧酸酯反应得到了一种光学活性的茎叶酮单羧酸酯衍生物，可用作合成光学活性茎曲烷衍生物的中间体。然后将这种衍生物经过酶催化的不对称脱醚羰基化反应。通过还原和脱水，从光学活性的茎叶酮单羧酸酯衍生物得到的无水异甘氨酸甲酯旋光方向与从天然可卡因中获得的无水异甘氨酸甲酯相同，证明获得的光学活性茎叶酮单羧酸酯衍生物具有与天然可卡因相同的绝对构型。从不对称脱醚羰基化反应中得到的光学活性茎叶酮单羧酸酯衍生物的产率为30至50摩尔％，其光学纯度为70至97％ ee。此外，还发现通过还原然后脱水，可以获得结晶的光学活性无水异甘氨酸羧酸酯衍生物，并且可以通过重结晶轻松提高其光学纯度。
• PROCESS FOR PRODUCING OPTICALLY ACTIVE TROPINONE MONOCARBOXYLIC ACID DERIVATIVE
  申请人：Nihon Medi-Physics Co., Ltd.

  公开号：EP1118674A1

  公开（公告）日：2001-07-25

  An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol%, and its optical purity was 70 to 97%ee. In addition, it was found that a crystalline optically active anhydroecgonine carboxylic acid ester derivative can be obtained by reducing and then dehydrating the optically active tropinonemonocarboxylic acid ester derivative and that its optical purity can easily be increased by recrystallization.

  将琥珀醛与有机胺和丙酮羧酸酯反应，得到一种具有光学活性的托品酮羧酸酯衍生物，然后将这种衍生物进行酶催化的不对称脱烷氧羰基化反应，得到一种具有光学活性的托品酮羧酸酯衍生物，这种衍生物可用作合成具有光学活性的托烷衍生物的中间体。由于通过还原和脱水从具有光学活性的托品酮一羧酸酯衍生物中得到的羟基可可碱甲酯与从天然可卡因中得到的羟基可可碱甲酯具有相同的旋光方向，因此证明所得到的具有光学活性的托品酮一羧酸酯衍生物与天然可卡因具有相同的绝对构型。通过不对称脱烷氧羰基化得到的具有光学活性的托品右旋羧酸酯衍生物的产率为 30 至 50 摩尔%，光学纯度为 70 至 97%ee。此外，研究还发现，通过还原然后脱水，可以得到结晶的光学活性安氢壬酸酯衍生物，而且其光学纯度很容易通过重结晶提高。
• Enantioselective Synthesis of Functionalized Tropanes by Rhodium(II) Carboxylate-Catalyzed Decomposition of Vinyldiazomethanes in the Presence of Pyrroles
  作者：Huw M. L. Davies、Julius J. Matasi、L. Mark Hodges、Nicholas J. S. Huby、Craig Thornley、Norman Kong、Jeffrey H. Houser

  DOI：10.1021/jo961920w

  日期：1997.2.1

  A series of enantiomerically enriched tropanes was synthesized by the rhodium(II) octanoate-catalyzed reaction of various N-BOC-protected pyrroles with vinyldiazomethanes. The overall 3 + 4 annulation occurs by a tandem cyclopropanation/Cope rearrangement. Asymmetric induction was best achieved in these transformations by using either (S)-lactate or (R)-pantolactone as a chiral auxiliary on the vinyldiazomethanes. Reactions carried out with the chiral catalyst tetrakis[N-( 4-tert-butylbenzenesulfonyl)-(L)-prolinato]dirhodium (2) provided moderate asymmetric induction, but also resulted in the formation of isomeric azabicyclooctane side products. The utility of the synthetic process was demonstrated through the asymmetric synthesis of(-)-anhydroecgonine methyl ester and (-)-ferruginine.
• US6486323B1
  申请人：——

  公开号：US6486323B1

  公开（公告）日：2002-11-26