benzyl (3S,4R)-3-hydroxy-4-(4-methoxyphenyl)pyrrolidine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: benzyl (3S,4R)-3-hydroxy-4-(4-methoxyphenyl)pyrrolidine-1-carboxylate
• 化学式: C₁₉H₂₁NO₄
• 分子量: 327.38
• InChiKey: GAQYKYRKPRYGCY-ZWKOTPCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (3S,4R)-3-hydroxy-4-(4-methoxyphenyl)pyrrolidine-1-carboxylate 在 吡啶 、 4-二甲氨基吡啶 、 Pseudomonas cepacia AK lipase 作用下， 以 phosphate buffer 、 二氯甲烷 、 甲苯 为溶剂， 反应 724.0h， 生成 benzyl (3S,4R)-3-acetyloxy-4-(4-methoxyphenyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis of conformationally restricted acetylcholine analogues. Comparing lipase-mediated resolution with simulated moving bed chromatography of arylated β-hydroxy-pyrrolidines

  摘要：

  The enantiodivergent synthesis of new, conformationally restricted acetylcholine analogues was accomplished using arylated endocyclic enecarbamates as key intermediates. Stereoselective hydroboration of the aryl enecarbamates provided the corresponding aryl-ss-hydroxy-pyrrolidines. Acetylation, deprotection, followed by N-bismethylation, led to the desired betaine products. The kinetic resolution of the intermediate alcohols was performed by lipase-mediated hydrolysis of its acetate derivatives, resulting in excellent enantioselectivities (E > 100). An enzymatic enantiopreference predicted by the Kazlauskas's model was confirmed following Riguera's protocol. Finally, chromatographic resolution of racemic alcohol 5a was evaluated by semi-preparative scale chiral simulated moving bed chromatography and its performance compared with biocatalysis. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2007.01.030
• 作为产物：
  描述：

  benzyl diallylcarbamate 在 palladium diacetate 、 Ru-based catalyst 2,6-二甲基吡啶 、 dimethyl sulfide borane 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 11.0h， 生成 benzyl (3S,4R)-3-hydroxy-4-(4-methoxyphenyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis of conformationally restricted acetylcholine analogues. Comparing lipase-mediated resolution with simulated moving bed chromatography of arylated β-hydroxy-pyrrolidines

  摘要：

  The enantiodivergent synthesis of new, conformationally restricted acetylcholine analogues was accomplished using arylated endocyclic enecarbamates as key intermediates. Stereoselective hydroboration of the aryl enecarbamates provided the corresponding aryl-ss-hydroxy-pyrrolidines. Acetylation, deprotection, followed by N-bismethylation, led to the desired betaine products. The kinetic resolution of the intermediate alcohols was performed by lipase-mediated hydrolysis of its acetate derivatives, resulting in excellent enantioselectivities (E > 100). An enzymatic enantiopreference predicted by the Kazlauskas's model was confirmed following Riguera's protocol. Finally, chromatographic resolution of racemic alcohol 5a was evaluated by semi-preparative scale chiral simulated moving bed chromatography and its performance compared with biocatalysis. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2007.01.030

文献信息

• Synthesis of conformationally restricted acetylcholine analogues. Comparing lipase-mediated resolution with simulated moving bed chromatography of arylated β-hydroxy-pyrrolidines
  作者：Ricardo de L. Barreto、Marcos J.S. Carpes、César C. Santana、Carlos R.D. Correia

  DOI：10.1016/j.tetasy.2007.01.030

  日期：2007.2

  The enantiodivergent synthesis of new, conformationally restricted acetylcholine analogues was accomplished using arylated endocyclic enecarbamates as key intermediates. Stereoselective hydroboration of the aryl enecarbamates provided the corresponding aryl-ss-hydroxy-pyrrolidines. Acetylation, deprotection, followed by N-bismethylation, led to the desired betaine products. The kinetic resolution of the intermediate alcohols was performed by lipase-mediated hydrolysis of its acetate derivatives, resulting in excellent enantioselectivities (E > 100). An enzymatic enantiopreference predicted by the Kazlauskas's model was confirmed following Riguera's protocol. Finally, chromatographic resolution of racemic alcohol 5a was evaluated by semi-preparative scale chiral simulated moving bed chromatography and its performance compared with biocatalysis. (c) 2007 Elsevier Ltd. All rights reserved.