(+/-)-Homoepibatidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (+/-)-Homoepibatidine
• 英文别名: (1S,5R,6R)-6-(6-chloropyridin-3-yl)-8-azabicyclo[3.2.1]octane
• 化学式: C₁₂H₁₅ClN₂
• 分子量: 222.718
• InChiKey: GDSORCYTZJIZHU-HBNTYKKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [11C]methyl iodide 、 (+/-)-Homoepibatidine 以 乙腈 为溶剂， 反应 0.17h， 以10%的产率得到(+/-)-[C-11]N-methylhomoepibatidine
  参考文献：
  名称：

  [C-11]N-methylhomoepibatidine: radiolabelling and biodistribution studies in mice

  摘要：

  The radiochemical synthesis of [C-11]N-methylhomoepibatidine (2) was accomplished by reacting homoepibatidine (1) and [C-11]iodomethane. The radiochemical yield was in the range of 5 to 10 % related to [C-ll]iodomethane. A high specific activity of 150 to 370 GBq/mu mol at the end of synthesis was achieved. The partition coefficient was log P-7.4 = 0.34. Biological evaluation was performed with the racemate in mice. High brain uptake was found. Compared to [C-11]N-methylepibatidine (4) data, which were achieved by the same experimental setup, the values of [C-11]N-methylhomoepibatidine (2) uptake in the brain were slightly lower (approximately 15 %/g compared to 20 %/g for [C-11]N-methylepibatidine (4)). But in contrast to the homologous [C-11]N-methylepibatidine (4) the brain uptake curve decreased after approximately 15 minutes showing reversible binding to the receptor. Pretreatment of mice with (-)-epibatidine (3) resulted in a considerably lower brain uptake while uptake in other tissues remained unchanged.

  DOI：

  10.1002/(sici)1099-1344(200002)43:2<127::aid-jlcr299>3.0.co;2-u
• 作为产物：
  描述：

  (1R,5R,6S)-6-羟基-8-甲基-8-氮杂双环[3.2.1]辛烷-3-酮 在 palladium diacetate 哌啶 、 吡啶 、 2,3,5-三甲基吡啶 、 氢氧化钾 、 甲酸 、 碘代三甲硅烷 、 4-甲基苯磺酸吡啶 、 potassium carbonate 、 对甲苯磺酸 、 一水合肼 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (+/-)-Homoepibatidine
  参考文献：
  名称：

  Synthesis and analgesic activity of Epibatidine analogues

  摘要：

  DOI：

  10.1016/0960-894x(96)00005-4

文献信息

• Synthesis of (±)-Epibatidine and Its Analogues
  作者：Donglu Bai、Rui Xu、Guohua Chu、Xingzu Zhu

  DOI：10.1021/jo9600666

  日期：1996.1.1

  (1), isolated from the skin of the Ecuadoran poison frog was synthesized in racemic form starting from tropinone. Distinctly different from the previously published approaches, this synthesis features the novel synthesis of the 7-azabicyclo[2.2.1]heptane ring system by contraction of the tropinone skeleton viaFavorskii rearrangement. Five analogues of 1 were also prepared, and their analgesic activities

  从厄瓜多尔毒蛙的皮肤中分离出的非鸦片止痛药Epibatidine（1）是从托皮酮开始以消旋形式合成的。与先前公开的方法截然不同，该合成的特征是通过Favorskii重排通过肌钙蛋白骨架的收缩来合成7-氮杂双环[2.2.1]庚烷环系统。还制备了5个1的类似物，并评估了它们的镇痛活性。
• Synthesis and nicotinic acetylcholine-binding properties of epibatidine homologues: homoepibatidine and dihomoepibatidine
  作者：John R. Malpass、David A. Hemmings、Anna L. Wallis、Stephen R. Fletcher、Shailendra Patel

  DOI：10.1039/b010178h

  日期：——

  Homoepibatidine 2 and dihomoepibatidine 3 have been synthesised from the 8-azabicyclo[3.2.1]oct-6-ene 8 and the 9-azabicyclo[4.2.1]oct-7-ene 9, respectively, the key precursors for reductive Heck coupling reactions. Alternative routes starting from cyclohepta- and cycloocta-1,3-diene are described; deoxygenation of tropane and homotropane epoxides provides a convenient route to 8 and 9. The enantiomers of 2 show similar potency at nicotinic receptors to the corresponding epibatidine enantiomers; the affinity of 3 is lower.

  高催眠素2和二高催眠素3已分别从8-氮杂双环[3.2.1]辛-6-烯8和9-氮杂双环[4.2.1]辛-7-烯9合成，它们是还原性Heck耦合反应的关键前体。描述了从环庚-1,3-二烯和环辛-1,3-二烯开始的替代路线；莨菪烷和同莨菪烷环氧化合物的脱氧作用为8和9提供了一条便捷的合成路线。2的对映异构体在烟碱受体上的效能与相应的催眠素对映异构体相似；3的亲和性较低。
• Synthesis of epibatidine homologues: Homoepibatidine and bis-homoepibatidine
  作者：John R Malpass、David A Hemmings、Anna L Wallis

  DOI：10.1016/0040-4039(96)00687-9

  日期：1996.5

  based, respectively, on the tropane (8-azabicyclo[3.2.1]octane) and homotropane (9-azabicyclo[4.2.1]nonane) ring systems. Epoxy- tropanes and -homotropanes (which are readily available from simple cyclic dienes) are convenient precursors for the azabicyclic alkenes needed for the key reductive coupling with pyridine derivatives.

  描述了合成方法，它们导致高乙哌啶和双高哌啶，它们分别基于环烷（8-氮杂双环[3.2.1]辛烷）和高乙烷（9-氮杂双环[4.2.1]壬烷）环系。环氧-托环烷和-同高环烷（可从简单的环状二烯容易获得）是与吡啶衍生物进行关键还原偶联所需的氮杂双环烯烃的便利前体。
• Patt, J. T.; Spang, J. E.; Westera, G., Journal of labelled compounds and radiopharmaceuticals, 1997, vol. 40, p. 528 - 530
  作者：Patt, J. T.、Spang, J. E.、Westera, G.、Schubiger, P. A.

  DOI：——

  日期：——
• [C-11]N-methylhomoepibatidine: radiolabelling and biodistribution studies in mice
  作者：J. T. Patt、J. E. Spang、G. Westera、P. A. Schubiger

  DOI：10.1002/(sici)1099-1344(200002)43:2<127::aid-jlcr299>3.0.co;2-u

  日期：2000.2

  The radiochemical synthesis of [C-11]N-methylhomoepibatidine (2) was accomplished by reacting homoepibatidine (1) and [C-11]iodomethane. The radiochemical yield was in the range of 5 to 10 % related to [C-ll]iodomethane. A high specific activity of 150 to 370 GBq/mu mol at the end of synthesis was achieved. The partition coefficient was log P-7.4 = 0.34. Biological evaluation was performed with the racemate in mice. High brain uptake was found. Compared to [C-11]N-methylepibatidine (4) data, which were achieved by the same experimental setup, the values of [C-11]N-methylhomoepibatidine (2) uptake in the brain were slightly lower (approximately 15 %/g compared to 20 %/g for [C-11]N-methylepibatidine (4)). But in contrast to the homologous [C-11]N-methylepibatidine (4) the brain uptake curve decreased after approximately 15 minutes showing reversible binding to the receptor. Pretreatment of mice with (-)-epibatidine (3) resulted in a considerably lower brain uptake while uptake in other tissues remained unchanged.