ethyl 2-benzyl-3-hydroxybutyrate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: ethyl 2-benzyl-3-hydroxybutyrate
• 英文别名: ethyl (2R,3S)-2-benzyl-3-hydroxybutyrate；(2R,3S)-ethyl-2-benzyl-3-hydroxybutanoate；ethyl (2R,3S)-2-benzyl-3-hydroxybutanoate
• 化学式: C₁₃H₁₈O₃
• 分子量: 222.284
• InChiKey: NKARQSGHMCQMJP-CMPLNLGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-benzyl-3-hydroxybutyrate 在 吡啶 、 癸醇 、 Candida antarctica immobilized lipase 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 792.0h， 生成 (2S,3R)-ethyl-2-benzyl-3-hydroxybutanoate
  参考文献：
  名称：

  对映异构纯的去外消旋顺式和反通过的Novozyme 435脂肪酶和它们的绝对构型的确定通过NMR光谱-α-β取代的羟基酯

  摘要：

  对映体纯的α-取代的β-羟基酯是配体，助剂和β-内酰胺类抗生素的重要手性结构单元。使用脂肪酶作为生物催化剂的两步化学酶促程序是合成此类产品的有效方法。迄今为止，所描述的方法限于不与外消旋甲醇相邻的手性中心的分子，此外，它们还限于酰化作用。这里，我们调查对映异构纯的去外消旋顺式-和反含有两个立体声中心-α-β取代的羟基酯，使用纯的条件和经典分子动力学（MD）模拟下的实验方法。对游离和固定化商业脂肪酶的筛选确定了来自南极假丝酵母的固定化脂肪酶B（Novozyme 435）是最适合空间需求的α-取代的β-羟基酯的生物催化剂。使用的Novozyme 435，反应条件进行了优化和羟基酯（3S）或（3R）与对映体过量达到≥99％实现EE和80％最大的总产率。对映体的绝对构型最终在用Mosher试剂（α-甲氧基-α-三氟甲基苯基乙酸= MTPA）衍生化后通过1 H-NMR光谱确定。

  DOI：

  10.1016/j.mcat.2021.111578
• 作为产物：
  描述：

  2-苄基乙酰乙酸乙酯 在 葡萄糖 、 calcium carbonate 、 sodium chloride 作用下， 以 水 为溶剂， 反应 120.0h， 以68%的产率得到ethyl 2-benzyl-3-hydroxybutyrate
  参考文献：
  名称：

  肺炎克雷伯菌 (NBRC 3319) 介导的 α-取代 β-氧代酯的不对称还原及其在小环碳环衍生物的对映选择性合成中的应用

  摘要：

  来自肺炎克雷伯菌 (NBRC 3319) 的酮还原酶选择性地还原几种 2-取代的 3-氧代丁酸乙酯，以产生具有显着立体控制的相应顺-β-羟基酯（de > 99 %，ee > 99 %）。对映体纯羟基氧代酯被合成操纵以获得新的小环碳环。

  DOI：

  10.1002/ejoc.201101695

文献信息

• The stereoselective α-alkylation of chiral β-hydroxy esters and some applications thereof
  作者：G. Fráter、U. Müller、W. Günther

  DOI：10.1016/s0040-4020(01)82413-3

  日期：1984.1

  The stereoselectivity of the α-alkylation of chiral β-hydroxy ester is discussed. The configuration of the alkylated product was proved chemically (Scheme 2). A one pot aldol-alkylation reaction was developed leading stereoselectively to racemic (s*,s*)-α-alkyl-β-hydroxy ester (Scheme 3,4). Baker's yeast reduction of 2-alkyl-3-keto ester led to valuable chiral (2RS,3S)-intermediates, which were converted

  讨论了手性β-羟基酯的α-烷基化的立体选择性。通过化学方法证明了烷基化产物的构型（方案2）。进行了一锅羟醛烷基化反应，立体选择性地生成了外消旋（s *，s *）-α-烷基-β-羟基酯（方案3,4）。贝克的2-烷基-3-酮酯的酵母还原反应产生了有价值的手性（2 RS，3 S）中间体，该中间体通过相应的二价阴离子转化为具有手性季C原子的化合物（方案6）。上述发现的合成应用显示在各种手性化合物的合成中（方案8和9）。
• A recombinant ketoreductase tool-box. Assessing the substrate selectivity and stereoselectivity toward the reduction of β-ketoesters
  作者：Dunming Zhu、Chandrani Mukherjee、J. David Rozzell、Spiros Kambourakis、Ling Hua

  DOI：10.1016/j.tet.2005.10.044

  日期：2006.1

  The substrate selectivity and stereoselectivity of a series of ketoreductases were evaluated toward the reduction of two sets of beta-ketoesters. Both the structural variety at beta-position and the substituent at alpha-position greatly affected the activity and stereoselectivity of these ketoreductases. For the first set of beta-ketoesters, at least one ketoreductase was found that catalyzed the formation of either (D) or (L) enantiomer of beta-hydroxyesters from each substrate with high optical purity, with the only exception of ethyl (D)-3-hydroxy3-phenylpropionate. For the second set of beta-ketoesters with alpha-substituents, the situation is more complex. More commonly, a ketoreductase was found that formed one of the four diastereomers in optically pure form, with only a few cases in which enzymes could be found that formed two or more of the diastereomers in high optical purity. The continued development of new, more diverse ketoreductases will create the capability to produce a wider range of single diastereomers of 2-substituted-3-hydroxy acids and their derivatives. (c) 2005 Elsevier Ltd. All rights reserved.
• Reversed Stereochemical Control in the Presence of CeCl₃ and TiCl₄ in the Lewis Acid Mediated Reduction of α-Alkyl-β-keto Esters by Metal Hydrides. A General Methodology for the Diastereoselective Synthesis of <i>s</i><i>yn</i>- and <i>a</i><i>nti</i>-α-Alkyl-β-hydroxy Esters
  作者：Enrico Marcantoni、Sara Alessandrini、Marco Malavolta、Giuseppe Bartoli、Maria Cristina Bellucci、Letizia Sambri、Renato Dalpozzo

  DOI：10.1021/jo9821574

  日期：1999.3.1

  The Lewis acid-mediated reduction of alpha-alkyl-beta-keto esters has been shown to proceed by different stereochemical control depending on the nature of the metal atom. Strongly chelating TiCl4 led to the syn isomer in high diastereomeric excess in noncoordinating solvents (CH2Cl2) at -78 degrees C with BH3. py as reducing agent, while nonchelating CeCl3 gave a high excess of the anti isomer in coordinating solvents (THF) at the same temperature with lithium triethylborohydride (LiEt3BH) as reducing agent. The methodology has been successfully utilized for obtaining important syn- and anti-alpha-alkyl-beta-hydroxy esters with high diastereoselectivity.
• Klebsiellapneumoniae (NBRC 3319) Mediated Asymmetric Reduction of α-Substituted β-Oxo Esters and Its Application to the Enantioiselective Synthesis of Small-Ring Carbocycle Derivatives
  作者：Rajib Bhuniya、Tridib Mahapatra、Samik Nanda

  DOI：10.1002/ejoc.201101695

  日期：2012.3

  Ketoreductases from Klebsiella pneumoniae (NBRC 3319) selectively reduce several 2-substituted ethyl 3-oxobutyrates to yield the corresponding syn-β-hydroxy esters with remarkable stereocontrol (de > 99 %, ee > 99 %). The enantiopure hydroxy oxo esters were synthetically manipulated to access new small-ring carbocycles.

  来自肺炎克雷伯菌 (NBRC 3319) 的酮还原酶选择性地还原几种 2-取代的 3-氧代丁酸乙酯，以产生具有显着立体控制的相应顺-β-羟基酯（de > 99 %，ee > 99 %）。对映体纯羟基氧代酯被合成操纵以获得新的小环碳环。
• Deracemization of diastereomerically pure syn- and anti-α-substituted β-hydroxyesters by Novozyme 435 lipase and determination of their absolute configuration by NMR spectroscopy
  作者：Christian Trapp、Kateřina Barková、Marek Jan Pecyna、Corinna Herrmann、Annett Fuchs、Dieter Greif、Martin Hofrichter

  DOI：10.1016/j.mcat.2021.111578

  日期：2021.6

  Enantiomerically pure α-substituted β-hydroxyesters are important chiral building blocks for ligands, auxiliaries and β-lactam antibiotics. A two-step chemo-enzymatic procedure using lipase as biocatalyst is an efficient way to synthesize such products. To date, the methods described are limited to molecules that do not contain a chiral center adjacent to the racemic carbinol, and furthermore, they

  对映体纯的α-取代的β-羟基酯是配体，助剂和β-内酰胺类抗生素的重要手性结构单元。使用脂肪酶作为生物催化剂的两步化学酶促程序是合成此类产品的有效方法。迄今为止，所描述的方法限于不与外消旋甲醇相邻的手性中心的分子，此外，它们还限于酰化作用。这里，我们调查对映异构纯的去外消旋顺式-和反含有两个立体声中心-α-β取代的羟基酯，使用纯的条件和经典分子动力学（MD）模拟下的实验方法。对游离和固定化商业脂肪酶的筛选确定了来自南极假丝酵母的固定化脂肪酶B（Novozyme 435）是最适合空间需求的α-取代的β-羟基酯的生物催化剂。使用的Novozyme 435，反应条件进行了优化和羟基酯（3S）或（3R）与对映体过量达到≥99％实现EE和80％最大的总产率。对映体的绝对构型最终在用Mosher试剂（α-甲氧基-α-三氟甲基苯基乙酸= MTPA）衍生化后通过1 H-NMR光谱确定。