cupreine

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 金鸡纳生物碱
• 英文名称: cupreine
• 英文别名: 9-epi-6'-hydroxycinchonidine；4-((1S)-hydroxy ((1S,4S,5R)-5-vinylquinuclidin-2 yl)methyl)quinolin-6-ol；4-[(S)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-hydroxymethyl]quinolin-6-ol
• 化学式: C₁₉H₂₂N₂O₂
• 分子量: 310.396
• InChiKey: VJFMSYZSFUWQPZ-OYUDYFSCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  56.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  cupreine 在 N-甲基吡咯烷酮 、 二月桂酸二丁基锡 、 caesium carbonate 作用下， 以 甲苯 为溶剂， 反应 49.0h， 生成 9-(tert-butylcarbamoyl)-6-neopentoxy-cinchonidine
  参考文献：
  名称：

  Elucidation of the Chiral Recognition Mechanism of Cinchona Alkaloid Carbamate-type Receptors for 3,5-Dinitrobenzoyl Amino Acids

  摘要：

  A cinchona alkaloid having extraordinary chiral discriminatory powers (alpha = 32.6 for dinitrobenzoyl leucine) is developed as a chiral stationary phase (CSP) for chromatography. An explanation of how chiral discrimination takes place is presented. Using a soluble analogue of the CSP, we found that NMR spectrometry indicates that 1:1 complexes exist for both optical isomers interacting with the CSP, that the free base form of the CSP exists in an open/closed ratio of 35/65 but that the protonated, bound-state form is exclusively in the anti-open conformation, and that significant intermolecular NOES exist for the more stable diastereomeric complex but not for the less stable complex. Stochastic molecular dynamics simulations were carried out in solvents of low and high dielectric. The chromatographic retention orders and free energy differences of analyte binding to CSP were reproduced computationally as were the observed intra-and intermolecular NOES. Data from the simulation were used to evaluate the intermolecular forces responsible for analyte binding as well as to discern fragments of the CSP doing most of the work of holding the complexes together. The enantiodifferentiating forces and the parts of the CSP most responsible for chiral discrimination are described. Moments of distributions of key dihedral angles and distances between centroids were used to assess the relative rigidity of the competing diastereomeric complexes. Simultaneous multiple-contact ion-pairing, hydrogen bonding, and pi-stacking are possible for the longer retained enantiomer only. An X-ray crystallographic study of the more stable complex confirms the conclusions derived from chromatography, NMR spectroscopy, and molecular modeling.

  DOI：

  10.1021/ja020203i
• 作为产物：
  描述：

  9-mesylquinine 在 D-酒石酸 、 sodium hydride 、 乙硫醇 作用下， 以 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 5.0h， 生成 cupreine
  参考文献：
  名称：

  金鸡纳生物碱衍生物催化β-酮酯的对映选择性α-羟基化

  摘要：

  在枯基氢过氧化物（CHP）存在下，实现了由铜吡啶催化的β-酮酯的高效α-羟基化。该反应适用于多种 β-酮酯，以高产率（高达 95%）得到具有优异对映选择性（高达 97% ee）的产物。该反应已成功放大到克级，并且 (S)-5-chloro-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate – 茚虫威的重要中间体在96% 收率和 86% ee。通过结晶可将对映体过量提高到99%，该方法具有对映选择性高、催化剂易于制备和催化剂回收等优点，具有工业应用前景。

  DOI：

  10.1055/s-0034-1378548
• 作为试剂：
  描述：

  (E)-1,2,4-trifluoro-3-(2-nitrovinyl)benzene 、 丙二酸二乙酯 在 cupreine 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以95%的产率得到diethyl (R)-2-(2-nitro-1-(2,3,6-trifluorophenyl)ethyl)malonate
  参考文献：
  名称：

  [EN] DOPAMINE-Β-HYDROXYLASE INHIBITORS
  [FR] INHIBITEURS DE DOPAMINE-B-HYDROXYLASE

  摘要：

  本发明涉及：(a) 公式I中的化合物（其中R1至R5和A如本文所定义）及其药用可接受的盐或溶剂，这些化合物可用作多巴胺-β-羟化酶抑制剂；(b) 包括这些化合物、盐或溶剂的药物组合物；(c) 使用这些化合物、盐或溶剂进行治疗；(d) 使用这些化合物、盐或溶剂进行治疗的治疗方法；以及(e) 用于合成这些化合物的过程和中间体。

  公开号：

  WO2020246903A1

文献信息

• Enantioselective α-Hydroxylation of β-Keto Esters Catalyzed by Cinchona Alkaloid Derivatives
  作者：Qingwei Meng、Yakun Wang、Zhi Li、Ting Xiong、Jingnan Zhao

  DOI：10.1055/s-0034-1378548

  日期：——

  A highly efficient α-hydroxylation of β-keto esters catalyzed by cupreidine in the presence of cumyl hydroperoxide (CHP) was achieved. The reaction was applied to a wide variety of β-keto esters to give products in high yields (up to 95%) with excellent enantioselectivities (up to 97% ee). The reaction had been successfully scaled up to a gram quantity and (S)-5-chloro-2-hydroxy-1-oxo-2,3-dihydro-

  在枯基氢过氧化物（CHP）存在下，实现了由铜吡啶催化的β-酮酯的高效α-羟基化。该反应适用于多种 β-酮酯，以高产率（高达 95%）得到具有优异对映选择性（高达 97% ee）的产物。该反应已成功放大到克级，并且 (S)-5-chloro-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate – 茚虫威的重要中间体在96% 收率和 86% ee。通过结晶可将对映体过量提高到99%，该方法具有对映选择性高、催化剂易于制备和催化剂回收等优点，具有工业应用前景。
• Enantioselective Phase-Transfer-Catalyzed Synthesis of Chiral <i>N</i>-Substituted 3,3-Dinitroazetidines by Aza-Michael Reaction
  作者：Hyo-Jun Lee、Chang-Woo Cho

  DOI：10.1021/acs.joc.5b02124

  日期：2015.11.20

  An efficient and highly enantioselective phase-transfer-catalyzed aza-Michael reaction of 3,3-dinitroazetidine, as N-centered nucleophile, to α,β-unsaturated ketones has been achieved using a quinidine-based phase-transfer catalyst (0.5–1 mol %), providing chiral N-substituted 3,3-dinitroazetidines in good yields (up to 99%) and excellent enantioselectivities (90–95% ee). This is the first example

  使用基于奎尼丁的相转移催化剂，已经实现了以N为中心的亲核试剂3,3-二硝基氮杂环丁烷对α，β-不饱和酮的高效且高度对映选择性的aza-Michael反应（0.5-1 mol％），以良好的收率（高达99％）和出色的对映选择性（90-95％ee）提供手性N-取代的3,3-二硝基氮杂环丁烷。这是在催化对映选择性氮杂-迈克尔反应中使用氮杂环丁烷作为N-中心亲核试剂的第一个例子。
• Prajer; Suszko, Roczniki Chemii, 1952, vol. 26, p. 555,558
  作者：Prajer、Suszko

  DOI：——

  日期：——
• Elucidation of the Chiral Recognition Mechanism of Cinchona Alkaloid Carbamate-type Receptors for 3,5-Dinitrobenzoyl Amino Acids
  作者：Norbert M. Maier、Sabine Schefzick、G. M. Lombardo、Miguel Feliz、Kari Rissanen、Wolfgang Lindner、Kenny B. Lipkowitz

  DOI：10.1021/ja020203i

  日期：2002.7.1

  A cinchona alkaloid having extraordinary chiral discriminatory powers (alpha = 32.6 for dinitrobenzoyl leucine) is developed as a chiral stationary phase (CSP) for chromatography. An explanation of how chiral discrimination takes place is presented. Using a soluble analogue of the CSP, we found that NMR spectrometry indicates that 1:1 complexes exist for both optical isomers interacting with the CSP, that the free base form of the CSP exists in an open/closed ratio of 35/65 but that the protonated, bound-state form is exclusively in the anti-open conformation, and that significant intermolecular NOES exist for the more stable diastereomeric complex but not for the less stable complex. Stochastic molecular dynamics simulations were carried out in solvents of low and high dielectric. The chromatographic retention orders and free energy differences of analyte binding to CSP were reproduced computationally as were the observed intra-and intermolecular NOES. Data from the simulation were used to evaluate the intermolecular forces responsible for analyte binding as well as to discern fragments of the CSP doing most of the work of holding the complexes together. The enantiodifferentiating forces and the parts of the CSP most responsible for chiral discrimination are described. Moments of distributions of key dihedral angles and distances between centroids were used to assess the relative rigidity of the competing diastereomeric complexes. Simultaneous multiple-contact ion-pairing, hydrogen bonding, and pi-stacking are possible for the longer retained enantiomer only. An X-ray crystallographic study of the more stable complex confirms the conclusions derived from chromatography, NMR spectroscopy, and molecular modeling.