(R)-quinuclidin-3-yl butyrate | 65732-89-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: (R)-quinuclidin-3-yl butyrate
• 英文别名: quinuclidin-3-yl butyrate；butyric acid ester of 3-quinuclidinol；Butanoic acid, (3R)-1-azabicyclo[2.2.2]oct-3-yl ester；[(3R)-1-azabicyclo[2.2.2]octan-3-yl] butanoate
• CAS: 65732-89-0
• 化学式: C₁₁H₁₉NO₂
• 分子量: 197.277
• InChiKey: BJNCVECKNVBHBP-JTQLQIEISA-N

物化性质

• 沸点：
  259.4±23.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-quinuclidin-3-yl butyrate 在 sodium carbonate 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以5.3 g的产率得到(R)-(-)-3-奎宁醇
  参考文献：
  名称：

  A practical chemoenzymatic process to access (R)-quinuclidin-3-ol on scale

  摘要：

  (+/-)-3-丁酰氧基奎宁环季铵盐丁酸盐6（2M，571g/L）由(+/-)-奎宁环-3-醇1和丁酸酐制得，经 fullNameAspergillus melleus fullName酶（1.0% w/v）在水溶液中进行不对称水解，同时加入Ca(OH)₂以维持反应pH7并固定由(+/-)-6引入且被酶解产生的丁酸。反应24小时后，用正庚烷萃取出(R)-奎宁环-3-基丁酸酯5a，其在甲醇中经Na₂CO₃甲氧基化后转化为(R)-1，这是作用于毒覃碱受体的神经调节剂的共同药效团，其对映体纯度为96%，总产率为从(+/-)-1的42%。不受欢迎的对映体(S)-1可通过正丁醇萃取并经其盐酸盐纯化，对映体纯度为89%，总产率为从(+/-)-1的40%。该对映体可通过Raney Co催化在含H气氛（5kg/cm²，140°C）下消旋化，以97%的产率再生(+/-)-1。(C)2003 Elsevier Science Ltd.版权归作者所有。

  DOI：

  10.1016/s0957-4166(03)00363-x
• 作为产物：
  描述：

  (R)-quinuclidin-3-yl butyrate butyric acid salt 在 水 、 sodium carbonate 作用下， 以 正己烷 为溶剂， 生成 (R)-quinuclidin-3-yl butyrate
  参考文献：
  名称：

  Simple one-pot process for the bioresolution of tertiary amino ester protic ionic liquids using subtilisin

  摘要：

  An efficient hydrolase-catalyzed bioresolution of tertiary amino ester protic ionic liquids has been demonstrated. Protic ionic liquids have been prepared in one step from the corresponding tertiary amino alcohols by treatment with butyric anhydride. After bioresolution, unreacted esters can be easily separated from the corresponding alcohols by extraction with hexane Bioresolution of quinuclidin-3-yl butyrate has been performed with excellent selectivity. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2009.09.007

文献信息

• A practical chemoenzymatic process to access (R)-quinuclidin-3-ol on scale
  作者：Fumiki Nomoto、Yoshihiko Hirayama、Masaya Ikunaka、Toru Inoue、Koutaro Otsuka

  DOI：10.1016/s0957-4166(03)00363-x

  日期：2003.7

  (+/-)-3-Butyryloxyquinuclidinium butyrate 6 (2 M, 571 g/L), prepared from (+/-)-quinuclidin-3-ol 1 and butyric anhydride, undergoes enantioselective hydrolysis by an Aspergillus melleus protease 1.0% (w/v)} in water in the presence of Ca(OH)(2) to keep the reaction at pH 7 and trap butyric acid that is introduced as part of (+/-)-6 and generated by the enzymatic hydrolysis. After a 24 h period, extraction with n-heptane provides (R)-quinuclidin-3-yl butyrate 5a, which, on methanolysis with Na2CO3, is converted into (R)-1, a common pharmacophore of neuromodulators acting on muscarinic receptors, in 96% ee and 42% overall yield from (+/-)-1. The unwanted antipode (S)-1, which is extracted into n-butanol and purified via its hydrochloride salt in 89% ee and 40% overall yield from (+/-)-1, can be racemized by the catalysis of Raney Co at 140degreesC under an atmosphere of H, (5 kg/cm(2)) to regenerate (+/-)-1 in 97% yield. (C) 2003 Elsevier Science Ltd. All rights reserved.

  (+/-)-3-丁酰氧基奎宁环季铵盐丁酸盐6（2M，571g/L）由(+/-)-奎宁环-3-醇1和丁酸酐制得，经 fullNameAspergillus melleus fullName酶（1.0% w/v）在水溶液中进行不对称水解，同时加入Ca(OH)₂以维持反应pH7并固定由(+/-)-6引入且被酶解产生的丁酸。反应24小时后，用正庚烷萃取出(R)-奎宁环-3-基丁酸酯5a，其在甲醇中经Na₂CO₃甲氧基化后转化为(R)-1，这是作用于毒覃碱受体的神经调节剂的共同药效团，其对映体纯度为96%，总产率为从(+/-)-1的42%。不受欢迎的对映体(S)-1可通过正丁醇萃取并经其盐酸盐纯化，对映体纯度为89%，总产率为从(+/-)-1的40%。该对映体可通过Raney Co催化在含H气氛（5kg/cm²，140°C）下消旋化，以97%的产率再生(+/-)-1。(C)2003 Elsevier Science Ltd.版权归作者所有。
• [EN] PROCESS FOR PRODUCING OPTICALLY ACTIVE ALCOHOL IN THE PRESENCE OF RHODIUM, A CHIRAL FERROCENYLDIPHOSPHINE AND AN OPTICALLY ACTIVE DIAMINE<br/>[FR] PROCEDE DE PRODUCTION D'UN ALCOOL OPTIQUEMENT ACTIF EN PRESENCE DE RHODIUM, FERROCENYLDIPHOSPHINE CHIRALE ET DIAMINE OPTIQUEMENT ACTIVE
  申请人：KAWAKEN FINE CHEMICALS CO

  公开号：WO2004078686A1

  公开（公告）日：2004-09-16

  A novel process for producing optically active alcohols through asymmetric hydrogenation of prochiral carbonyl compounds allows high-yield, industrially favorable production of an optically active alcohol at a high enantiomeric excess. The process is charaterized in that the asymmetric hydrogenation is carried out in the absence of a base and in the presence of a rhodium complex or a salt thereof; an optically active ferrocenyl diphosphine; and an optically active diamine.

  通过对具有手性氢化合物的不对称氢化，可以通过一种新型工艺生产光学活性醇，实现高产率、工业上有利的光学活性醇生产，其旋光异构体过量高。该工艺的特点是，在无碱存在的情况下，采用铑配合物或其盐；光学活性二膦基二茂铁；以及光学活性二胺进行不对称氢化。
• ENZYME FOR THE PRODUCTION OF OPTICALLY PURE 3-QUINUCLIDINOL
  申请人：CADILA HEALTHCARE LIMITED

  公开号：US20140147896A1

  公开（公告）日：2014-05-29

  The present invention provides a process for production of optically pure quinuclidinol of formula-(I) by reduction of quinuclidinone of formula-(II) in presence of suitable oxidoreductase enzyme derived from Saccharomyces species. Formula (II, I) Moreover, the present enzyme works in presence of cofactor NADP where the cofactor is regenerated by suitable system. The present invention also provides a recombinant vector containing genes co expressing suitable polypeptides having oxido-reductase activity and polypeptide having capacity to regenerate the co-factor. The said vector is transformed in suitable host cell.

  本发明提供了一种生产光学纯的公蝉烷醇(I式)的方法，该方法通过在Saccharomyces物种中引入适当的氧化还原酶酶来还原公蝉酮(II式)。公式(II, I)此外，本酶在NADP辅因子存在下工作，该辅因子由适当的系统再生。本发明还提供了一种重组载体，其中包含共表达适当的具有氧化还原酶活性的多肽和具有再生辅因子能力的多肽的基因。所述载体被转化到适当的宿主细胞中。
• Enantiomeric enrichment of (R,S)-3-quinuclidinol
  申请人：BEND RESEARCH, INC.

  公开号：EP0577253A2

  公开（公告）日：1994-01-05

  A method for the enantiomeric enrichment of 3-quinuclidinol is disclosed which comprises an initial step of acid anhydride esterification of the alcohol, followed by preferential enzymatic hydrolysis of one enantiomer with a subtilisin protease.

  本发明公开了一种富集 3-quinuclidinol 对映体的方法，包括对醇进行酸酐酯化的初始步骤，然后用枯草蛋白酶对其中一种对映体进行优先酶水解。
• Influence of the Acyl Moiety on the Hydrolysis of Quinuclidinium Esters Catalyzed by Butyrylcholinesterase
  作者：Ines Primožič、Srđanka Tomić

  DOI：10.5562/cca1829

  日期：——

  Eight chiral esters of quinuclidin-3-ol and butyric, acetic, pivalic and benzoic acid were synthesized as well as their racemic and chiral, quaternary N-benzyl derivatives. All racemic and chiral quaternary compounds were studied as substrates and/or inhibitors of horse serum butyrylcholinesterase (BChE). The best substrate for the enzyme was (R)-N-benzyl butyrate. The rates of hydrolysis decreased in order (R)-butyrate >> (R)-acetate (7-fold slower) > (R)-pivalate (8-fold slower) > (R)-benzoate (9-fold slower reaction), while (S)-N-benzyl esters were much poorer substrates (320 (butyrate) - 4360-fold slower (pivalate) than the appropriate (R)-enantiomer). For all (S)-N-benzyl esters excluding (S)-N-benzyl acetate inhibition constants were determined (K-a = 3.3-60 mu mol dm(-3)). The hydrolysis of racemic mixtures of N-benzyl esters proceeded 1.4 (for acetate) - 5.1 (for benzoate) times slower than that of pure (R)-enantiomers of the corresponding concentrations due to the inhibition with (S)-enantiomers. Change of the acyl moiety of the substrate effected both activity and stereoselectivity of the BChE.(doi: 10.5562/cca1829)