2-[(3R,4S,6S)-6-[(R)-[tert-butyl(dimethyl)silyl]oxy-(6-methoxyquinolin-4-yl)methyl]-1-azabicyclo[2.2.2]octan-3-yl]ethanol | 183994-18-5

• 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: 2-[(3R,4S,6S)-6-[(R)-[tert-butyl(dimethyl)silyl]oxy-(6-methoxyquinolin-4-yl)methyl]-1-azabicyclo[2.2.2]octan-3-yl]ethanol
• CAS: 183994-18-5
• 化学式: C₂₆H₄₀N₂O₃Si
• 分子量: 456.701
• InChiKey: UYLYUXIPSUOOPU-QXVOXHNYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  54.82
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-[(3R,4S,6S)-6-[(R)-[tert-butyl(dimethyl)silyl]oxy-(6-methoxyquinolin-4-yl)methyl]-1-azabicyclo[2.2.2]octan-3-yl]ethanol 在 4-二甲氨基吡啶 、 jones reagent 、 四丁基氟化铵 、 三乙胺 、 2,6-二氯苯甲酰氯 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Macrocycles Derived from Cinchona Alkaloids:  A Thermodynamic vs Kinetic Study

  摘要：

  Cyclization of the quiuine-derived monomer (2a): HO-Cq-OMe, under thermodynamic control, gives mainly cyclic trimer Cq(3) (7a), whereas kinetic cyclization of the similar monomer HO-Cq-OH (8) gives a mixture of cyclic products. This difference in product distribution is attributed to predisposition of the monomer unit, which means the building block adopts a more stable conformation in cyclic trimer than it can in cyclic tetramer. The reversibility of the thermodynamic reaction was demonstrated using electrospray mass spectrometry to monitor the catalyzed mixing of the two cyclic trimers Cq(3) (7a) and Cc(3) (7b), which results in the statistically expected 1:3:3:1 ratio of all possible cyclic trimers Cc(3):Cc(2)Cq:CeCq(2):Cq(3).

  DOI：

  10.1021/jo971813h
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 在 4-二甲氨基吡啶 、 硼烷四氢呋喃络合物 、 十二/十四烷基二甲基氧化胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 2-[(3R,4S,6S)-6-[(R)-[tert-butyl(dimethyl)silyl]oxy-(6-methoxyquinolin-4-yl)methyl]-1-azabicyclo[2.2.2]octan-3-yl]ethanol
  参考文献：
  名称：

  Macrocycles Derived from Cinchona Alkaloids:  A Thermodynamic vs Kinetic Study

  摘要：

  Cyclization of the quiuine-derived monomer (2a): HO-Cq-OMe, under thermodynamic control, gives mainly cyclic trimer Cq(3) (7a), whereas kinetic cyclization of the similar monomer HO-Cq-OH (8) gives a mixture of cyclic products. This difference in product distribution is attributed to predisposition of the monomer unit, which means the building block adopts a more stable conformation in cyclic trimer than it can in cyclic tetramer. The reversibility of the thermodynamic reaction was demonstrated using electrospray mass spectrometry to monitor the catalyzed mixing of the two cyclic trimers Cq(3) (7a) and Cc(3) (7b), which results in the statistically expected 1:3:3:1 ratio of all possible cyclic trimers Cc(3):Cc(2)Cq:CeCq(2):Cq(3).

  DOI：

  10.1021/jo971813h

文献信息

• Building thermodynamic combinatorial libraries of quinine macrocycles
  作者：Stuart J. Rowan、Jeremy K. M. Sanders

  DOI：10.1039/a703291i

  日期：——

  Thermodynamically-controlled transesterification of a predisposed cinchonidine building block with a more flexible extended quinine monomer leads to a combinatorial mixture of 11 macrocyclic receptors which is analysed by electrospray mass spectrometry; similar results with alkaloid–cholate mixtures demonstrate the generality of the approach.

  通过热力学控制，预先设定的金鸡纳啶结构单元与更灵活的扩展奎宁单体发生酯交换反应，产生了 11 种大环受体的组合混合物，并通过电喷雾质谱法对其进行了分析；生物碱-胆酸盐混合物的类似结果表明了这种方法的通用性。
• Effects of Shape on Thermodynamic Cyclizations of Cinchona Alkaloids
  作者：Stuart J. Rowan、Dominic J. Reynolds、Jeremy K. M. Sanders

  DOI：10.1021/jo982496x

  日期：1999.8.1

  Thermodynamic cyclizations of a series of cinchona alkaloid derivatives are investigated. An extended quinine monomer 2:HO-Ce-OMe is prepared and cyclized to produce a mixture of cyclic oligomers. Combining the extended monomer 2:HO-Ce-OMe with the previously reported cinchonidine monomer 1b:HO-Cc-OMe under thermodynamic control produces a library of quinine-derived macrocycles. Two quinidine-derived methyl ester monomers 10:HO-Cd-OMe and 16:HO-Ca-OMe are also reported. Both are preorganized to form cyclic dimers; upon carrying out the thermodynamic cyclization on a mixture of both monomers only a small percentage (5%) of the hetero-dimer is obtained. Thermodynamic cyclization of the corresponding cinchonidine derived methyl ester 1b:HO-Cc-OMe with 10:HO-Cd-OMe results in the self-sorting of the two diastereoisomers.
• A novel artemisinin–quinine hybrid with potent antimalarial activity
  作者：John J. Walsh、David Coughlan、Nicola Heneghan、Caroline Gaynor、Angus Bell

  DOI：10.1016/j.bmcl.2007.04.054

  日期：2007.7

  Artemisinin was reduced to dihydroartemisinin and coupled to a carboxylic acid derivative of quinine via an ester linkage. This novel hybrid molecule had potent activity against the 3D7 and (drug-resistant) FcB1 strains of Plasmodium falciparum? in culture. The activity was superior to that of artemisinin alone, quinine alone, or a 1:1 mixture of artemisinin and quinine. (c) 2007 Elsevier Ltd. All rights reserved.
• Rowan, Stuart J.; Brady, Paul A.; Sanders, Jeremy K. M., Angewandte Chemie, 1996, vol. 108, # 18, p. 2283 - 2285
  作者：Rowan, Stuart J.、Brady, Paul A.、Sanders, Jeremy K. M.

  DOI：——

  日期：——