(2S,3S)-2-benzylquinuclidin-3-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (2S,3S)-2-benzylquinuclidin-3-ol
• 英文别名: cis-2-Benzyl-chinuclidinol-(3)；(2S,3S)-2-benzyl-1-azabicyclo[2.2.2]octan-3-ol
• 化学式: C₁₄H₁₉NO
• 分子量: 217.311
• InChiKey: COLQHXANZSDSJL-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,5-二甲基溴苄 、 (2S,3S)-2-benzylquinuclidin-3-ol 在 双(三甲基硅烷基)氨基钾 作用下， 生成 cis-2-benzyl-3-<(3,5-dimethylbenzyl)oxy>-1-azabicyclo<2.2.2>octane
  参考文献：
  名称：

  Identification of a Series of 3-(Benzyloxy)-1-azabicyclo[2.2.2]octane Human NK1 Antagonists

  摘要：

  The synthesis and in vitro and in vivo evaluation of a series of 3-(benzyloxy)-1-azabicyclo[2.2.2]octane NK1 antagonists are described. While a number of 3,5-disubstituted benzyl ethers afford high affinity, the 3,5-bis(trifluoromethyl)benzyl was found to combine high in vitro affinity with good oral activity. Detailed structure-activity relationship studies in conjunction with data from molecular modeling and mutagenesis work have allowed the construction of a model of the pharmacophore. Specific interactions that have been identified include an interaction between His-197 and one of the rings of the benzhydryl, a Lipophilic pocket containing His-265 that the benzyl ether occupies, and a possible hydrogen bond between Gln-165 and the oxygen of the benzyl ether.

  DOI：

  10.1021/jm00024a007
• 作为产物：
  描述：

  3-奎宁环酮盐酸盐 在 5%-palladium/activated carbon 、 [(R,R)-N-(2-amino-1,2-diphenylethyl)pentafluorobenzenesulfonamide]chloride(p-cymene)ruthenium (II) 、 氢气 、 甲酸铵 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 20.0~50.0 ℃ 、101.33 kPa 条件下， 反应 84.5h， 生成 (2S,3S)-2-benzylquinuclidin-3-ol
  参考文献：
  名称：

  钌催化的DKR不对称转移氢化反应对顺3-喹啉的高选择性合成。

  摘要：

  描述了一种通过动态动力学拆分通过Ru催化的不对称转移氢化对映体选择性合成顺-3-奎宁环醇的方法。反应在温和的条件下进行，使用甲酸铵作为氢供体，以高收率（高达99：1 dr）和对映选择性（95-99％ee）提供高收率（最高99％）的产物。该方案适用于通过简单的重结晶具有完美对映选择性的克级制备。

  DOI：

  10.1021/acs.orglett.0c01361

文献信息

• Method for producing optically active quinuclidinols having one or more substituted groups at the 2-position
  申请人：Katayama Takeaki

  公开号：US20080081911A1

  公开（公告）日：2008-04-03

  The invention provides a method for producing optically active 3-quinuclidinols having one or more substituted groups at the 2-position; wherein 3-quinuclidinones having one or more substituted groups at the 2-position are reacted with compounds providing hydrogen in the presence of a certain metal complex.

  本发明提供了一种制备在2位具有一个或多个取代基的光学活性3-喹诺啉醇的方法；其中，在特定金属配合物的存在下，将在2位具有一个或多个取代基的3-喹诺酮与提供氢的化合物反应。
• 一种奎宁醇的制备方法
  申请人：东莞市东阳光动物保健药品有限公司

  公开号：CN112707899A

  公开（公告）日：2021-04-27

  本发明涉及一种奎宁醇的制备方法，属于药物化学领域；所述方法包括酮化合物在甲酸铵和催化剂条件下，制备得到单一构型的醇化合物；本发明提供的方法，选择性高，收率高，纯度高，易于应用和实施。
• Enantioselective PTC: Varying the cinchona alkaloid motive
  作者：Eckehard Volker Dehmlow、Stefan Wagner、Achim Müller

  DOI：10.1016/s0040-4020(99)00210-0

  日期：1999.5

  Enantiopure phase transfer catalysts 3a-j, 4a-j, 5, 8a-j, 9a,b, 10a,b were prepared which represent changes in the fundamental structure of the alkaloids. These were tested in three enantioselective model reactions. It turned out that both the quinoline group carrying side arm and the quinuclidine core are important features of PT catalysts for highly enantioselective reactions. (C) 1999 Elsevier Science Ltd. All rights reserved.
• 2-(Arylmethyl)-3-substituted quinuclidines as selective α7 nicotinic receptor ligands
  作者：Anatoly Mazurov、Jozef Klucik、Lan Miao、Teresa Y. Phillips、Angela Seamans、Jeffrey D. Schmitt、Terry A. Hauser、Raymond T. Johnson、Craig Miller

  DOI：10.1016/j.bmcl.2005.02.045

  日期：2005.4

  A series of 2-(arylmethyl)-3-substituted quinuclidines was developed as alpha 7 neuronal nicotinic acetylcholine receptor (nAChR) agonists based on a putative pharmacophore model. The series is highly selective for the alpha 7 over other nAChRs (e.g., the alpha A beta 2 of the CNS, and the muscle and ganglionic subtypes) and is functionally tunable at alpha 7. One member of the series, (+)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzo[b]furan-2-carboxamide (+)-81), has potent agonistic activity for the alpha 7 nAChR (EC50 = 33 nM, I-max = 1.0), at concentrations below those that result in desensitization. (c) 2005 Elsevier Ltd. All rights reserved.
• Identification of a Series of 3-(Benzyloxy)-1-azabicyclo[2.2.2]octane Human NK1 Antagonists
  作者：Christopher J. Swain、Eileen M. Sewart、Margaret A. Cascieri、Tung M. Fong、Richard Herbert、D Euan MacIntyre、Kevin J. Merchant、Simon N. Owen、Andrew P. Owens

  DOI：10.1021/jm00024a007

  日期：1995.11

  The synthesis and in vitro and in vivo evaluation of a series of 3-(benzyloxy)-1-azabicyclo[2.2.2]octane NK1 antagonists are described. While a number of 3,5-disubstituted benzyl ethers afford high affinity, the 3,5-bis(trifluoromethyl)benzyl was found to combine high in vitro affinity with good oral activity. Detailed structure-activity relationship studies in conjunction with data from molecular modeling and mutagenesis work have allowed the construction of a model of the pharmacophore. Specific interactions that have been identified include an interaction between His-197 and one of the rings of the benzhydryl, a Lipophilic pocket containing His-265 that the benzyl ether occupies, and a possible hydrogen bond between Gln-165 and the oxygen of the benzyl ether.