2-(2-propanoyl)-8-azabicyclo<3.2.1>oct-2-ene | 155930-77-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(2-propanoyl)-8-azabicyclo<3.2.1>oct-2-ene
• 英文别名: 2-propionyl-8-azabicyclo<3.2.1>octa-2-ene；2-propanoyl-8-azabicyclo<3.2.1>oct-2-ene；1-(8-Azabicyclo[3.2.1]oct-2-en-2-yl)propan-1-one
• CAS: 155930-77-1
• 化学式: C₁₀H₁₅NO
• 分子量: 165.235
• InChiKey: GVXDYDXTVANUAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(2-propanoyl)-8-azabicyclo<3.2.1>oct-2-ene 在 copper bromide-dimethyl sulfide 、 sodium cyanoborohydride 作用下， 以 乙醚 、 水 、 乙腈 为溶剂， 反应 4.25h， 生成 3β-cyclohexyl-8-methyl-2β-propanoyl-8-azabicyclo<3.2.1>octane
  参考文献：
  名称：

  Synthesis of 2.beta.-Acyl-3.beta.-aryl-8-azabicyclo[3.2.1]octanes and Their Binding Affinities at Dopamine and Serotonin Transport Sites in Rat Striatum and Frontal Cortex

  摘要：

  A novel entry to tropane analogs of cocaine was developed on the basis of the reaction of rhodium-stabilized vinylcarbenoids with pyrroles. These analogs were tested:in binding to dopamine and serotonin (5-HT) transporters in:membranes from rat striatum and frontal cortex. In all the analogs, the aryl group at the 3-position was directly bound to the tropane ring (as in WIN-35,428), and methyl or ethyl ketone moieties were present at the a-position instead of the typical ester group. The series of analogs containing a 2-naphthyl group at the 3-position were most potent, with K-i values < 1 nM in binding to both dopamine and 5-HT transporters. Although the unsubstituted 2-naphthyl analog was nonselective at dopamine and 5-HT transport sites, other compounds:were selective for either site. In general, compounds with relatively small substituents on the aromatic moiety (such as p-methyl or p-fluoro) were relatively selective for the dopamine transporters, while a p-isopropylphenyl derivative was selective:for the 5-HT transport sites. This latter compound represents the first N-methyltropane derivative specific for 5-HT transporters. Resolution of two of the most significant analogs was achieved by HPLC on a chiral stationary phase; the active enantiomer of a 2-naphthyl analog exhibited K-i values of <0.1 nM at both dopamine and 5-HT transporter sites.

  DOI：

  10.1021/jm00035a005
• 作为产物：
  描述：

  5-己烯-3-酮 在 RhCl(PPh₃)3 rhodium(II) octanoate 、 4-乙酰氨基苯磺酰叠氮 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三氟乙酸 作用下， 以 乙醇 、 正己烷 、 二氯甲烷 、 乙腈 为溶剂， 25.0 ℃ 、310.27 kPa 条件下， 反应 14.0h， 生成 2-(2-propanoyl)-8-azabicyclo<3.2.1>oct-2-ene
  参考文献：
  名称：

  Synthesis of 2.beta.-Acyl-3.beta.-aryl-8-azabicyclo[3.2.1]octanes and Their Binding Affinities at Dopamine and Serotonin Transport Sites in Rat Striatum and Frontal Cortex

  摘要：

  A novel entry to tropane analogs of cocaine was developed on the basis of the reaction of rhodium-stabilized vinylcarbenoids with pyrroles. These analogs were tested:in binding to dopamine and serotonin (5-HT) transporters in:membranes from rat striatum and frontal cortex. In all the analogs, the aryl group at the 3-position was directly bound to the tropane ring (as in WIN-35,428), and methyl or ethyl ketone moieties were present at the a-position instead of the typical ester group. The series of analogs containing a 2-naphthyl group at the 3-position were most potent, with K-i values < 1 nM in binding to both dopamine and 5-HT transporters. Although the unsubstituted 2-naphthyl analog was nonselective at dopamine and 5-HT transport sites, other compounds:were selective for either site. In general, compounds with relatively small substituents on the aromatic moiety (such as p-methyl or p-fluoro) were relatively selective for the dopamine transporters, while a p-isopropylphenyl derivative was selective:for the 5-HT transport sites. This latter compound represents the first N-methyltropane derivative specific for 5-HT transporters. Resolution of two of the most significant analogs was achieved by HPLC on a chiral stationary phase; the active enantiomer of a 2-naphthyl analog exhibited K-i values of <0.1 nM at both dopamine and 5-HT transporter sites.

  DOI：

  10.1021/jm00035a005

文献信息

• Synthesis of 3β-Aryl-8-azabicyclo[3.2.1]octanes with High Binding Affinities and Selectivities for the Serotonin Transporter Site
  作者：Huw M. L. Davies、Lisa A. Kuhn、Craig Thornley、Julius J. Matasi、Tammy Sexton、Steven R. Childers

  DOI：10.1021/jm9600508

  日期：1996.1.1

  A novel entry to tropane analogs of cocaine was developed based on the reaction of rhodium-stabilized vinylcarbenoids with pyrroles. These analogs were tested in binding to dopamine, serotonin (5-HT), and norepinephrine transporters in membranes from rat striatum and frontal cortex. In all the analogs, the aryl group at the 3 position was directly bound to the tropane ring and an ethyl ketone moiety

  基于铑稳定的乙烯基类胡萝卜素与吡咯的反应，开发了可卡因的托烷类似物的新型产品。测试了这些类似物与大鼠纹状体和额叶皮膜中的多巴胺，5-羟色胺（5-HT）和去甲肾上腺素转运蛋白的结合。在所有类似物中，在3位上的芳基直接与托烷环结合并且在2位上存在乙基酮部分。通过适当地修饰芳基和氮取代基，制备了高效的和5-HT选择性的托烷。最有效和选择性最大的化合物是3β-[4-（1-甲基乙烯基）苯基] -2β-丙酰基-8-氮杂双环[3.2.1]辛烷（13b），Ki为0。
• 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.
• Synthesis of iodinated 3β-aryltropanes with selective binding to either the dopamine or serotonin transporters
  作者：Huw M.L Davies、Pingda Ren、Norman X Kong、Tammy Sexton、Steven R Childers

  DOI：10.1016/s0960-894x(02)00048-3

  日期：2002.3

  Iodinated 3beta-aryltropanes functionalized appropriately at the 2beta-, 8- and aryl positions display selective binding to either the dopamine or serotonin transporters. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthesis and monoamine transporter affinity of 3β-(4-(2-pyrrolyl)phenyl)-8-azabicyclo[3.2.1]octanes and 3β-(5-Indolyl)-8-azabicyclo[3.2.1]octanes
  作者：Huw M.L Davies、Pingda Ren、Norman Kong、Tammy Sexton、Steven R Childers

  DOI：10.1016/s0960-894x(00)00701-0

  日期：2001.2

  3 beta-(5-Indolyl)-8-azabicyclo[3.2.1]octanes display potent binding affinity for both the dopamine and serotonin transporters, while certain 3 beta-(4-(2-pyrrolyl)phenyl)-8-azabicyclo[3.2.1]octanes selectively bind to the serotonin transporter. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Synthesis of 2.beta.-Acyl-3.beta.-aryl-8-azabicyclo[3.2.1]octanes and Their Binding Affinities at Dopamine and Serotonin Transport Sites in Rat Striatum and Frontal Cortex
  作者：Huw M. L. Davies、Elie Saikali、Nicholas J. S. Huby、Vernon J. Gilliatt、Julius J. Matasi、Tammy Sexton、Steven R. Childers

  DOI：10.1021/jm00035a005

  日期：1994.4

  A novel entry to tropane analogs of cocaine was developed on the basis of the reaction of rhodium-stabilized vinylcarbenoids with pyrroles. These analogs were tested:in binding to dopamine and serotonin (5-HT) transporters in:membranes from rat striatum and frontal cortex. In all the analogs, the aryl group at the 3-position was directly bound to the tropane ring (as in WIN-35,428), and methyl or ethyl ketone moieties were present at the a-position instead of the typical ester group. The series of analogs containing a 2-naphthyl group at the 3-position were most potent, with K-i values < 1 nM in binding to both dopamine and 5-HT transporters. Although the unsubstituted 2-naphthyl analog was nonselective at dopamine and 5-HT transport sites, other compounds:were selective for either site. In general, compounds with relatively small substituents on the aromatic moiety (such as p-methyl or p-fluoro) were relatively selective for the dopamine transporters, while a p-isopropylphenyl derivative was selective:for the 5-HT transport sites. This latter compound represents the first N-methyltropane derivative specific for 5-HT transporters. Resolution of two of the most significant analogs was achieved by HPLC on a chiral stationary phase; the active enantiomer of a 2-naphthyl analog exhibited K-i values of <0.1 nM at both dopamine and 5-HT transporter sites.