(+)-(1R)-2-(trifluoromethanesulfonyloxy)-9-azabicyclo[4.2.1]non-2-ene-9-carboxylic acid ethyl ester | 281650-63-3

• 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)-2-(trifluoromethanesulfonyloxy)-9-azabicyclo[4.2.1]non-2-ene-9-carboxylic acid ethyl ester
• 英文别名: ethyl (1R,6R)-2-(trifluoromethylsulfonyloxy)-9-azabicyclo[4.2.1]non-2-ene-9-carboxylate
• CAS: 281650-63-3
• 化学式: C₁₂H₁₆F₃NO₅S
• 分子量: 343.324
• InChiKey: RJPPNGDJXDVCAN-RKDXNWHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (+)-(1R)-2-(trifluoromethanesulfonyloxy)-9-azabicyclo[4.2.1]non-2-ene-9-carboxylic acid ethyl ester 在 lithium chloride copper(l) iodide 、 二(氰基苯)二氯化钯 、 碘代三甲硅烷 、 三苯胂 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 (1R)-2-(4-pyridazinyl)-9-azabicyclo[4.2.1]non-2-ene
  参考文献：
  名称：

  新型（2-氯-5-吡啶基）-9-氮杂双环[4.2.1] non-2-ene UB-165的对映纯二嗪类似物的合成及烟碱结合研究。

  摘要：

  作为我们计划的一部分，该计划旨在优化毒性影响之外的治疗效果（如在自然存在的烟碱乙酰胆碱受体调节剂中观察到的（-）-烟碱，（-）-依巴替丁，（-）-铁精氨酸和（+）-毒素A） ），我们研究了（+）-毒素A型结构领域中二嗪的生物甾体潜力。在deschloro-UB-165（DUB-165，6）的二嗪类似物系列中，3-吡啶基药效基团被4-吡啶并嗪基，5-嘧啶基或2-吡嗪基部分生物等位取代产生了新的nAChR配体7 ，8和9。钯催化的3-diethylboranylpyridine（14）的Suzuki交联和相应的三丁基锡烷基二嗪15-17与N保护的9-氮杂双环[的三氟甲磺酸乙烯酯13]的Stille交联。 4.2。1] nonan-2-one 12构成这些对映纯的抗毒素类化合物6-9的合成关键步骤。通过放射性配体结合测定法对（α4）（2）（β2）（3），α3β4和α7nAChR亚型的体外亲和力研

  DOI：

  10.1021/jm010936y
• 作为产物：
  描述：

  (5S)-8-methyl-8-azabicyclo[3.2.1]octan-2-one 在 三甲基铝 、 双(三甲基硅烷基)氨基钾 、 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 甲苯 、 苯 为溶剂， 反应 31.0h， 生成 (+)-(1R)-2-(trifluoromethanesulfonyloxy)-9-azabicyclo[4.2.1]non-2-ene-9-carboxylic acid ethyl ester
  参考文献：
  名称：

  A new and efficient synthetic route to enantiopure (+)-anatoxin-a from (−)-cocaine hydrochloride

  摘要：

  The potent nAChR agonist (+)-anatoxin-a was efficiently synthesized in enantiomerically pure form starting from a readily available confiscated grade (-)-cocaine hydrochloride. The eight-step synthesis providing novel extensions to existing methodology proceeded with 26% overall yield and with stereochemical integrity of the relevant original stereogenic centers. Key steps were an effective ring expansion of the (+)-2-tropinone 2 to the 9-azabicyclo[4.2.1]nonanone 5 with TMSCHN2/Al(CH3)(3) and the introduction of the required methyl ketone side chain in masked form by reacting the corresponding enol triflate 6 with ethyl vinyl ether/Pd(OAc2) under Heck reaction conditions. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00059-8

文献信息

• 3D QSAR Analyses-Guided Rational Design of Novel Ligands for the (α4)₂(β2)₃ Nicotinic Acetylcholine Receptor
  作者：Holger Gohlke、Simone Schwarz、Daniela Gündisch、Maria Cristina Tilotta、Alexander Weber、Thomas Wegge、Gunther Seitz

  DOI：10.1021/jm020859m

  日期：2003.5.1

  Three-dimensional quantitative structure-activity relationship methods, the comparative molecular field analysis (CoMFA) and the comparative molecular similarity indices analysis (CoMSIA), were applied using a training set of 45 ligands of the (alpha4)(2)(beta2)(3) nicotinic acetylcholine receptor (nAChR). All compounds are related to (-)-epibatidine, (-)-cytisine, (+)-anatoxin-a, and (-)-ferruginine, and additionally, novel diazabicyclo[4.2.1]nonane- and quinuclidin-2-ene-based structures were included. Their biological data have been determined by utilizing the same experimental protocol. Statistically reliable models of good predictive power (CoMFA r(2) = 0.928, q(2) = 0.692, no. of components = 3; CoMSIA r(2) = 0.899, q(2) = 0.701, no. of components = 3) were achieved. The results obtained were graphically interpreted in terms of field contribution maps. Hence, physicochemical. determinants of binding, such as steric and electrostatic and, for the first time, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor properties, were mapped back onto the molecular structures of a set of nAChR modulators. In particular, changes in the binding affinity of the modulators as a result of modifications in the aromatic ring systems could be rationalized by the steric, electrostatic, hydrophobic, and hydrogen bond acceptor properties. These results were used to guide the rational design of new nAChR ligands such as 48-52 and 54, which were subsequently synthesized for the first time and tested. Key steps of our synthetic approaches were successfully applied Stille and Suzuki cross-coupling reactions. Predictive r(2) values of 0.614 and 0.660 for CoMFA and CoMSIA, respectively, obtained for 22 in part previously unknown ligands for the (alpha4)(2)(beta2)(3) subtype, demonstrate the high quality of the 3D QSAR models.
• Synthesis and Nicotinic Binding Studies on Enantiopure Diazine Analogues of the Novel (2-Chloro-5-pyridyl)-9-azabicyclo[4.2.1]non-2-ene UB-165
  作者：Holger Gohlke、Daniela Gündisch、Simone Schwarz、Gunther Seitz、Maria Cristina Tilotta、Thomas Wegge

  DOI：10.1021/jm010936y

  日期：2002.2.1

  bioisosteric potential of diazines in the field of (+)-anatoxin-a-type structures. In the series of diazine analogues of deschloro-UB-165 (DUB-165, 6), bioisosteric replacement of the 3-pyridyl pharmacophoric element by a 4-pyridazinyl, 5-pyrimidinyl, or 2-pyrazinyl moiety resulted in novel nAChR ligands 7, 8, and 9. A palladium-catalyzed Suzuki cross-coupling of the 3-diethylboranylpyridine (14) and

  作为我们计划的一部分，该计划旨在优化毒性影响之外的治疗效果（如在自然存在的烟碱乙酰胆碱受体调节剂中观察到的（-）-烟碱，（-）-依巴替丁，（-）-铁精氨酸和（+）-毒素A） ），我们研究了（+）-毒素A型结构领域中二嗪的生物甾体潜力。在deschloro-UB-165（DUB-165，6）的二嗪类似物系列中，3-吡啶基药效基团被4-吡啶并嗪基，5-嘧啶基或2-吡嗪基部分生物等位取代产生了新的nAChR配体7 ，8和9。钯催化的3-diethylboranylpyridine（14）的Suzuki交联和相应的三丁基锡烷基二嗪15-17与N保护的9-氮杂双环[的三氟甲磺酸乙烯酯13]的Stille交联。 4.2。1] nonan-2-one 12构成这些对映纯的抗毒素类化合物6-9的合成关键步骤。通过放射性配体结合测定法对（α4）（2）（β2）（3），α3β4和α7nAChR亚型的体外亲和力研
• A new and efficient synthetic route to enantiopure (+)-anatoxin-a from (−)-cocaine hydrochloride
  作者：Thomas Wegge、Simone Schwarz、Gunther Seitz

  DOI：10.1016/s0957-4166(00)00059-8

  日期：2000.4

  The potent nAChR agonist (+)-anatoxin-a was efficiently synthesized in enantiomerically pure form starting from a readily available confiscated grade (-)-cocaine hydrochloride. The eight-step synthesis providing novel extensions to existing methodology proceeded with 26% overall yield and with stereochemical integrity of the relevant original stereogenic centers. Key steps were an effective ring expansion of the (+)-2-tropinone 2 to the 9-azabicyclo[4.2.1]nonanone 5 with TMSCHN2/Al(CH3)(3) and the introduction of the required methyl ketone side chain in masked form by reacting the corresponding enol triflate 6 with ethyl vinyl ether/Pd(OAc2) under Heck reaction conditions. (C) 2000 Elsevier Science Ltd. All rights reserved.