(R)-3-acetyloxy-4-(4-methylbenzyloxy)-butanenitrile | 922735-36-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-3-acetyloxy-4-(4-methylbenzyloxy)-butanenitrile
• 英文别名: (R)-1-cyanomethyl-2-[(4-methylbenzyl)oxy]ethyl acetate；(2R)-1-Cyano-3-[(4-methylphenyl)methoxy]propan-2-yl acetate；[(2R)-1-cyano-3-[(4-methylphenyl)methoxy]propan-2-yl] acetate
• CAS: 922735-36-2
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: KPZKFDBGWDLCNI-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (+/-)-1-cyanomethyl-2-[(4-methylbenzyl)oxy]ethyl acetate 在 Novozym 435 作用下， 生成 (S)-3-acetoxy-4-(4-methylbenzyloxy)-butanenitrile 、 (R)-3-acetyloxy-4-(4-methylbenzyloxy)-butanenitrile 、 (R)-4-(4-methylbenzyl)oxy-3-hydroxybutanenitrile
  参考文献：
  名称：

  Elaboration on the access to (S)-4-(4-methylbenzyl)oxy-3-hydroxybutanenitrile, a key intermediate for statins, by combining the kinetic resolution of racemate and the recycle of undesired enantiomer

  摘要：

  High enantioselectivity (E94) was observed in Candida antarctica lipase B-catalyzed hydrolysis of the corresponding acetate of racemic title compound. The reaction rate of the slow (S)-isomer was effectively suppressed by lowering the reaction temperature from 25 degrees C to 5 degrees C, to allow a five times increase of the enantioselectivity. The ee of the (S)-isomer, reached 97.8% at the reasonable conversion (52%) as the unreacted recovery, and the repetition of the enzymatic reaction provided pure enantiomer. The undesired (R)-isomer was oxidized with IBX and reduced with whole-cell biocatalysis with Candida floricola JCM 9439 to (S)-isomer (63.2% ee), which serves as the enantiomerically enriched substrate for further lipase-catalyzed resolution. The combination of total processes provided over 50% yield of the pure (S)-isomer, exceeding the theoretical limit for the enantiomeric resolution of racemate. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2010.02.008

文献信息

• Efficient lipase-catalyzed kinetic resolution of 4-arylmethoxy-3-hydroxybutanenitriles: application to an expedient synthesis of a statin intermediate
  作者：Fenglai Sun、Gang Xu、Jianping Wu、Lirong Yang

  DOI：10.1016/j.tetasy.2006.10.037

  日期：2006.11

  The kinetic resolution of 4-arylmethoxy-3-hydroxybutanenitriles was investigated by lipase-catalyzed transesterification in organic solvents. A high enantio selectivity was obtained via reaction with vinyl acetate in a mixed solvent (n-heptane/acetonitrile 1:1), which was catalyzed by the lipase from Artgribacter sp. A better selectivity was demonstrated when the number of substituents on the aryl ring increased. (S)-4-Arylmethoxy-3-hydroxybutanenitriles can be obtained with enantiomeric excesses of up to 98.0% by this method. Furthermore we have developed a novel route to synthesize tert-butyl (S)-6-benzyloxy-5-hydroxy-3-oxohexanoate, a key intermediate for the preparation of HMG-CoA reductase inhibitors (statins). (c) 2006 Elsevier Ltd. All rights reserved.
• Elaboration on the access to (S)-4-(4-methylbenzyl)oxy-3-hydroxybutanenitrile, a key intermediate for statins, by combining the kinetic resolution of racemate and the recycle of undesired enantiomer
  作者：Maki Sakamoto、Manabu Hamada、Toshinori Higashi、Mitsuru Shoji、Takeshi Sugai

  DOI：10.1016/j.molcatb.2010.02.008

  日期：2010.6

  High enantioselectivity (E94) was observed in Candida antarctica lipase B-catalyzed hydrolysis of the corresponding acetate of racemic title compound. The reaction rate of the slow (S)-isomer was effectively suppressed by lowering the reaction temperature from 25 degrees C to 5 degrees C, to allow a five times increase of the enantioselectivity. The ee of the (S)-isomer, reached 97.8% at the reasonable conversion (52%) as the unreacted recovery, and the repetition of the enzymatic reaction provided pure enantiomer. The undesired (R)-isomer was oxidized with IBX and reduced with whole-cell biocatalysis with Candida floricola JCM 9439 to (S)-isomer (63.2% ee), which serves as the enantiomerically enriched substrate for further lipase-catalyzed resolution. The combination of total processes provided over 50% yield of the pure (S)-isomer, exceeding the theoretical limit for the enantiomeric resolution of racemate. (C) 2010 Elsevier B.V. All rights reserved.