(E)-methyl 5-methyl-3-cyanohex-2-enoate | 1248544-41-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (E)-methyl 5-methyl-3-cyanohex-2-enoate
• 英文别名: (E)-methyl 3-cyano-5-methylhex-2-enoate；methyl (E)-3-cyano-5-methylhex-2-enoate
• CAS: 1248544-41-3
• 化学式: C₉H₁₃NO₂
• 分子量: 167.208
• InChiKey: GEMUYRCTNJLMSN-VMPITWQZSA-N

物化性质

• 沸点：
  250.1±23.0 °C(Predicted)
• 密度：
  0.996±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-methyl 5-methyl-3-cyanohex-2-enoate 在 葡萄糖 、 Old Yellow Enzyme-3 、 重水 、 还原型辅酶Ⅰ 作用下， 以 aq. phosphate buffer 、 异丙醇 为溶剂， 反应 24.0h， 以91%的产率得到
  参考文献：
  名称：

  Rationalisation of the stereochemical outcome of ene-reductase-mediated bioreduction of α,β-difunctionalised alkenes

  摘要：

  The OYE1-3-mediated reductions of some alpha,beta-difunctionalised alkenes, showing on the double bond a nitrile and ester group, are submitted to a careful stereochemical analysis, in order to identify which of the two electron-withdrawing groups (EWGs) is responsible for the activation of the C=C double bond towards reduction and for establishing hydrogen bond interactions within the binding pocket of the enzymes. The results show that for most of these substrates the activating EWG is the CN moiety linked to the prostereogenic olefinic carbon atom. The final stereochemical outcome can be explained through the empirical model which has been recently developed for difunctionalised alkenes activated by carbonyl/carboxyl containing EWGs.In a single case the activation is due to the COOR group linked to the less substituted olefinic carbon atom: an alternative empirical model is established for this kind of substrates, taking into consideration the OYE-catalysed reductions of beta,beta'-disubstituted-a-monofunctionalised alkenes. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2013.12.020
• 作为产物：
  描述：

  4-甲基-2-氧代戊腈 在 正丁基锂 、 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 18.5h， 生成 (E)-methyl 5-methyl-3-cyanohex-2-enoate
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF ( S ) - 3 - CYANO - 5 - METHYLHEXANOIC ACID DERIVATIVES ADN OF PREGABALIN
  [FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS D'ACIDE (S)-3-CYANO-5-MÉTHYLHEXANOÏQUE ET DE PRÉGABALINE

  摘要：

  这项发明提供了一种利用酶催化还原公式(I)化合物的制备过程，其中所述化合物为公式(lla)或llb)的化合物。公式(I)的化合物可用于制备普拉巴林。

  公开号：

  WO2012025861A1

文献信息

• Nickel/Lewis Acid-Catalyzed Cyanoesterification and Cyanocarbamoylation of Alkynes
  作者：Yasuhiro Hirata、Akira Yada、Eiji Morita、Yoshiaki Nakao、Tamejiro Hiyama、Masato Ohashi、Sensuke Ogoshi

  DOI：10.1021/ja102346v

  日期：2010.7.28

  nickel/Lewis acid (LA) cooperative catalysis to give beta-cyano-substituted acrylates and acrylamides, respectively, in highly stereoselective and regioselective manners. The resulting adducts serve as versatile synthetic building blocks through chemoselective transformations of the ester, amide, and cyano groups as demonstrated by the synthesis of typical structures of beta-cyano ester, beta-amino

  发现氰基甲酸酯和氰基甲酰胺通过镍/路易斯酸 (LA) 协同催化在炔烃上加成，分别以高度立体选择性和区域选择性的方式生成 β-氰基取代的丙烯酸酯和丙烯酰胺。由此产生的加合物通过酯、酰胺和氰基的化学选择性转化作为通用的合成构件，如β-氰基酯、β-氨基腈、γ-内酰胺、双取代马来酸酐和γ的典型结构的合成所证明的-氨基丁酸。另一方面，发现氰基甲酸酯硫酯和苯甲酰氰的相关反应在钯/LA 催化剂存在下通过脱羰在炔烃上加成。
• NAD(P)H-Independent Asymmetric CC Bond Reduction Catalyzed by Ene Reductases by Using Artificial Co-substrates as the Hydrogen Donor
  作者：Christoph K. Winkler、Dorina Clay、Marcello Entner、Markus Plank、Kurt Faber

  DOI：10.1002/chem.201303897

  日期：2014.1.27

  To develop a nicotinamide‐independent single flavoenzyme system for the asymmetric bioreduction of CC bonds, four types of hydrogen donor, encompassing more than 50 candidates, were investigated. Six highly potent, cheap, and commercially available co‐substrates were identified that (under the optimized conditions) resulted in conversions and enantioselectivities comparable with, or even superior

  为了开发一种不依赖烟酰胺的单黄素酶系统，用于 CC 键的不对称生物还原，研究了四种类型的氢供体，包括 50 多个候选者。确定了六种高效、廉价且可商购的共底物（在优化条件下），其转化率和对映选择性与传统的双酶烟酰胺腺嘌呤二核苷酸磷酸 (NAD(P) H)-回收系统。
• Nitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases
  作者：Christoph K. Winkler、Dorina Clay、Nikolaus G. Turrini、Horst Lechner、Wolfgang Kroutil、Simon Davies、Sebastien Debarge、Pat O'Neill、Jeremy Steflik、Mike Karmilowicz、John W. Wong、Kurt Faber

  DOI：10.1002/adsc.201301055

  日期：2014.5.26

  Asymmetric bioreduction of an (E)‐β‐cyano‐2,4‐dienoic acid derivative by ene‐reductases allowed a shortened access to a precursor of pregabalin [(S)‐3‐(aminomethyl)‐5‐methylhexanoic acid] possessing the desired configuration in up to 94% conversion and >99% ee. Deuterium labelling studies showed that the nitrile moiety was the preferred activating/anchor group in the active site of the enzyme over

  的（非对称的生物还原Ë由烯还原酶）-β氰基-2,4-二烯酸衍生物允许缩短访问普瑞巴林的前体[（小号）-3-（氨基甲基）-5-甲基己酸]拥有该所需配置高达94％的转化率和> 99％的ee。氘标记研究表明，相对于羧酸或相应的甲酯，腈部分是酶活性位点中的首选活化/锚定基团。
• Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases
  作者：Christoph K. Winkler、Dorina Clay、Simon Davies、Pat O’Neill、Paul McDaid、Sebastien Debarge、Jeremy Steflik、Mike Karmilowicz、John W. Wong、Kurt Faber

  DOI：10.1021/jo302484p

  日期：2013.2.15

  The asymmetric bioreduction of a library of beta-cyanoacrylate esters using ene-reductases was studied with the aim to provide a biocatalytic route to precursors for GABA analogues, such as pregabalin. The stereochemical outcome could be controlled by substrate-engineering through size-variation of the ester moiety and by employing stereochemically pure (E)- or (Z)-isomers, which allowed to access both enantiomers of each product in up to quantitative conversion in enantiomerically pure form. In addition, stereoselectivities and conversions could be improved by mutant variants of OPR1, and the utility of the system was demonstrated by preparative-scale applications.