(R)-4-phenyl-2-butyl acetate | 129098-41-5

• 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)-4-phenyl-2-butyl acetate
• 英文别名: (R)-4-phenylbutan-2-yl acetate；(R)-4-Phenyl-2-acetoxybutane；[(2R)-4-phenylbutan-2-yl] acetate
• CAS: 129098-41-5
• 化学式: C₁₂H₁₆O₂
• 分子量: 192.258
• InChiKey: IVEWTAOGAGBQGG-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-4-phenyl-2-butyl acetate 在 NADPH 、 nicotinamide adenine dinucleotide phosphate 、 W₁₁₀A/I₈₆A/C₂₉₅A TeSADH 、 水 、 potassium hydroxide 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 (S)-(+)-4-苯基-2-丁醇
  参考文献：
  名称：

  Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase mutants with improved racemization activity

  摘要：

  Controlled racemization of enantiopure alcohols is a key step in dynamic kinetic resolution. We recently reported the racemization of enantiopure phenyl-ring-containing alcohols using W110A Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase (W110A TeSADH), which relies on selectivity mistakes. Trp-110 lines the large pocket of the active site of TeSADH, which allows W110A TeSADH mutant to accommodate phenyl-ring-containing substrates in Prelog mode, albeit with selectivity mistakes. Here, we report the racemization of enantiopure phenyl-ring-containing alcohols using several Trp-110 mutants of TeSADH in the presence of the oxidized and reduced forms of nicotinamide adenine dinucleotide. We observed a noticeable enhancement in racemization efficiency when W110G TeSADH was used compared with W110Q, W110M, W110L, W110I, and W110V. This observation was anticipated because the W110G mutation is expected to open the large pocket of the active site to a greater extent compared to other mutants of TeSADH at W110. Both enantiomers of 1-phenyl-2-propanol and 4-phenyl-2-butanol were fully racemized by W110G TeSADH. We also constructed a triple mutant of TeSADH, W110A/186A/C295A, by site-directed mutagenesis with the aim of opening the two pockets of the active site of TeSADH. The W110A/186A/C295A mutant was employed to racemize enantiopure phenyl-ring-containing alcohols. The current study demonstrates that W110G and W110A/186A/C295A TeSADH are more efficient catalysts for the racemization of enantiopure secondary alcohols than the previously reported mutant W110A TeSADH [6]. (C) 2015 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2015.02.012
• 作为产物：
  描述：

  4-苯基-2-丁醇 在 吡啶 、 Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase W₁₁₀A mutant 、 烟酰胺腺嘌呤双核苷酸磷酸盐 作用下， 以 丙酮 为溶剂， 反应 30.0h， 生成 (R)-4-phenyl-2-butyl acetate
  参考文献：
  名称：

  使用单个酒精脱氢酶对仲醇进行脱硝

  摘要：

  我们开发了一种单酶介导的两步法来对仲醇进行脱脂。乙醇嗜热厌氧菌仲醇脱氢酶的单个突变体能够使外消旋醇非立体选择性氧化为酮，然后进行立体选择性还原过程。改变丙酮和2-丙醇共底物的量分别控制连续氧化和还原反应的立体选择性。我们使用一种酶完成了仲醇的脱硝作用，一锅中的ee高达99％以上，回收率达到99.5％以上，而无需分离前手性酮中间体。

  DOI：

  10.1002/cctc.201600160

文献信息

• Concerted Catalytic Reactions for Conversion of Ketones or Enol Acetates to Chiral Acetates
  作者：Hyun M. Jung、Jeong H. Koh、Mahn-Joo Kim、Jaiwook Park

  DOI：10.1021/ol9914043

  日期：2000.2.1

  [reaction: see text] Enol acetates or ketones asymmetrically transformed to chiral acetates in high yields with high optical purities through multistep reactions catalyzed by a lipase and a ruthenium complex. 2,6-Dimethylheptan-4-ol was chosen as a suitable hydrogen donor, and 4-chlorophenyl acetate was used as an acyl donor for the conversion of ketones.

  [反应：见正文]通过脂肪酶和钌络合物催化的多步反应，烯醇乙酸酯或酮以高收率和高光学纯度不对称地转化为手性乙酸酯。选择2，6-二甲基庚烷-4-醇作为合适的氢供体，并且使用乙酸4-氯苯酯作为用于酮转化的酰基供体。
• Formamides as Lewis Base Catalysts in S_NReactions-Efficient Transformation of Alcohols into Chlorides, Amines, and Ethers
  作者：Peter H. Huy、Sebastian Motsch、Sarah M. Kappler

  DOI：10.1002/anie.201604921

  日期：2016.8.16

  and waste‐balance (E‐factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee). In a practical one‐pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac‐Clopidogrel and S‐Fendiline.

  简单的甲酰胺催化剂可促进以苯甲酰氯为唯一试剂将醇类有效转化为烷基氯。这些亲核取代是通过亚胺基活化的醇作为中间体进行的。这种新颖的方法甚至可以在无溶剂条件下进行，其特点是具有出色的官能团耐受性，可扩展性（> 100 g）和废物平衡（电子因子低至2）。手性底物的转化具有优异的立体化学转化水平（99％→≥95％ee）。在实际的一锅法中，初步形成的氯化物可以进一步转化为胺，叠氮化物，醚，硫化物和腈。该方法的价值在药物rac ‐ Clopidogrel和S‐芬迪林。
• Core-Shell Composite as the Racemization Catalyst in the Dynamic Kinetic Resolution of Secondary Alcohols
  作者：Jie Wang、Dong-Minh Do、Gaik-Khuan Chuah、Stephan Jaenicke

  DOI：10.1002/cctc.201200566

  日期：2013.1

  thickness were synthesized and used as racemization catalysts in the one‐pot dynamic kinetic resolution (DKR) of secondary alcohols by using lipase‐catalyzed transesterification. The inert Silicalite‐1 shell covered the external acidic sites of the Beta zeolite core, suppressing dehydration and non‐enantioselective transesterification of the alcohol. The alcohols could penetrate the Silicalite‐1 shell

  合成了具有可控壳厚度的Beta–Silicalite-1核壳微复合材料，并通过脂肪酶催化的酯交换反应，将其用作消旋催化剂，用于仲醇的一锅动力学动力学拆分（DKR）。惰性Silicalite-1壳覆盖了Beta沸石核的外部酸性位，从而抑制了醇的脱水和非对映选择性酯交换。醇可能会穿透Silicalite-1壳，进入Beta核心的酸性位点进行消旋作用，但是，由于酶的形成（R）-酯的尺寸较大，因此被排除在外。结果，（R的高ee）保留了酯类产品，并将脱水副产物减至最少。由于复合外消旋催化剂的形状选择特性，可以在酶催化的酯交换反应中使用较小且易于获得的酰基供体，以获得高对映体纯度的酯。使用优化的核壳催化剂CS-60，将1-苯基乙醇与乙酸异丙烯酯的DKR形成酯的选择性为92％，并以94％ee形成所需的（R）-1-苯基乙酸乙酯。
• Evaluation of<i>gem</i>-Diacetates as Alternative Reagents for Enzymatic Regio- and Stereoselective Acylation of Alcohols
  作者：Dominik Koszelewski、Anna Brodzka、Arleta Madej、Damian Trzepizur、Ryszard Ostaszewski

  DOI：10.1021/acs.joc.1c00154

  日期：2021.5.7

  used as sustainable acyl donors for enzymatic acylation of chiral and nonchiral alcohols. Especially, it was revealed that geminal diacetates showed higher reactivity than vinyl acetate for hydrolases that are sensitive to acetaldehyde. Under optimized conditions for enzymatic acylation, several synthetically relevant saturated and unsaturated acetates of various primary alcohols were obtained in very

  双乙酸双乙酸酯已被用作可持续的酰基供体，用于手性和非手性醇的酶促酰化。特别是，据透露，孪位二乙酸酯表现出比对于对乙醛敏感水解乙酸乙烯酯反应性更高。在优化的酶促酰化条件下，可以以高达98％的极高收率获得几种合成相关的各种伯醇的饱和和不饱和乙酸酯，而无需双键的E / Z异构化。随后，从所得的醛中重新生成酰基供体，并在酰化中不断重复使用。因此，所开发的方法的特征在于高原子效率。此外，还显示了使用双子胺的酰化作用通过区分1-苯基-1,3-丙二醇中的伯羟基和仲羟基，二乙酸酯可产生显着的区域选择性，从而以高收率仅提供3-乙酰氧基-1-苯基-丙烷-1-醇。此外，酶动力学拆分（EKR）和酶化学动态动力学拆分（DKR）协议使用被开发偕二乙酸作为酰化剂，产生的手性乙酸盐以高收率高达94％与对映体过量超过99％。
• Dual enzymatic dynamic kinetic resolution by Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase and Candida antarctica lipase B
  作者：Ibrahim Karume、Musa M. Musa、Odey Bsharat、Masateru Takahashi、Samir M. Hamdan、Bassam El Ali

  DOI：10.1039/c6ra18895h

  日期：——

  showed that this racemization approach in organic solvent was compatible with Candida antarctica lipase B (CALB)-catalyzed kinetic resolution. This compatibility, therefore, allowed a dual enzymatic dynamic kinetic resolution of racemic alcohols using CALB-catalyzed kinetic resolution and W110A TeSADH-catalyzed racemization of phenyl-ring-containing alcohols.

  溶胶-凝胶法固定化乙醇嗜热厌氧菌仲醇脱氢酶（TeSADH）使其可以在有机介质中外消旋对映纯醇。在这里，我们报道了使用干凝胶固定的W110A TeSADH在己烷中而不是在酶所需的水性介质中消旋对映体纯的含苯环的仲醇。我们进一步表明，这种在有机溶剂中的消旋方法与南极假丝酵母脂肪酶B（CALB）催化的动力学拆分相容。因此，这种相容性允许使用CALB催化的动力学拆分和W110A TeSADH催化的含苯环的醇的消旋化作用，使消旋醇具有双重酶促动力学拆分。