octyl (R)-2-bromo-2-phenylacetate

• 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: octyl (R)-2-bromo-2-phenylacetate
• 英文别名: (R)-2-bromo-2-phenylacetic acid octyl ester；(R)-2-bromophenylacetic acid octyl ester；octyl (2R)-2-bromo-2-phenylacetate
• 化学式: C₁₆H₂₃BrO₂
• 分子量: 327.261
• InChiKey: RILZCENGSUVURH-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  19
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (+/-)-2-bromo-2-phenylacetic acid octyl ester 在 lipase from carica papaya latex 作用下， 以 癸烷 为溶剂， 生成 S-2-溴-2-苯基乙酸 、 octyl (R)-2-bromo-2-phenylacetate
  参考文献：
  名称：

  Lipase from Carica papaya latex presents high enantioselectivity toward the resolution of prodrug (R,S)-2-bromophenylacetic acid octyl ester

  摘要：

  Besides the well-known papain, lipolytic activity is another interesting enzymatic activity present in latex from Carica papaya. This lipolytic activity is strongly attached to the latex solid phase, resulting in a naturally immobilized biocatalyst. In this work we describe the kinetic resolution of (R,S)-2-bromophenylacetic acid octyl ester by Carica papaya crude latex and two partially purified latex fractions. Several parameters, such as substrate concentration and solvent effects were studied. The best results were obtained using decane as solvent with 50 mM of substrate and 50 mg/mL enzyme/reaction medium; under these conditions, a high enantioselectivity (E >200) was obtained with crude latex. A twofold increase of the initial rate maintaining E >200 was obtained using purified fractions without protease and without esterase. Lipase from Carica papaya latex is the most enantioselective wild-type enzyme ever described for the studied reaction. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.07.151

文献信息

• Towards a novel explanation of Pseudomonas cepacia lipase enantioselectivity via molecular modelling of the enantiomer trajectory into the active site
  作者：David Guieysse、Christophe Salagnad、Pierre Monsan、Magali Remaud-Simeon、Vinh Tran

  DOI：10.1016/s0957-4166(03)00374-4

  日期：2003.7

  slower-reacting enantiomers have equivalent potential energies and most of them possess the hydrogen bonds essential for catalysis. On this basis, it is not possible to distinguish the diastereomeric complexes. The second approach is original and consists in a simple but robust protocol of pseudomolecular dynamics simulations under constraints to map the probable trajectory of the enantiomers in the active

  在正辛烷中（RS）-2-溴苯基乙酸乙酯与1-辛醇之间的酯交换反应中，洋葱假单胞菌脂肪酶对（R-异构体是57。描述了两种策略来研究参与该酶对映选择性的结构基础。模仿过渡态的四面体中间体的分子模型能够鉴定出每种对映异构体的两种潜在生产性底物结合模式。然而，用反应快和慢的对映异构体获得的构象具有相等的势能，并且它们大多数具有催化必不可少的氢键。在此基础上，不可能区分非对映异构体。第二种方法是原始方法，它包含一个简单但鲁棒的伪分子动力学模拟方案，该方案在约束条件下绘制活性部位对映异构体的可能轨迹。对于快速反应的对映异构体，总是发现酶/底物的相互作用能较低，这令人满意地证实了实验结果。能量差异归因于这些底物与衬砌通路的疏水性残基网络的特定相互作用。此外，机制细节表明，疏水残基的枢转侧链以协调的步进齿轮运动起作用，其基本作用是选择并引导底物朝向活性位点。使用这种脂肪酶，这种动态特征可能是对此尚未开发的
• Lipase-catalyzed enantioselective transesterification toward esters of 2-bromo-tolylacetic acids
  作者：David Guieysse、Christophe Salagnad、Pierre Monsan、Magali Remaud-Simeon

  DOI：10.1016/s0957-4166(02)00784-x

  日期：2003.2

  Lipases from Candida antarctica, Pseudomonas cepacia and Rhizomucor miehei were tested in the resolution of seven racemic substrates belonging to the (RS)-2-bromo tolyl acetate ester category, but differing either in the position of the methyl substituent on the acyl part of the aromatic ring, or in the structure of the alkyl group. Lipase-catalyzed kinetic resolution via transesterification reaction between the ester and octanol in octane revealed that, of the three enzymes tested, P. cepacia lipase is the most efficient for resolution of the various racemates, with R-enantiopreference. In addition, the position of the methyl substituent was found to play a key role in governing the enantioselectivity of the reaction. Using P. cepacia lipase and 2-bromo-in/p-tolyl- or 2-bromophenylacetic acid esters E-values of >50 were measured, whereas with the ortho derivatives, E-values dramatically decreased to <6. (C) 2003 Elsevier Science Ltd. All rights reserved.
• New efficient lipase from Yarrowia lipolytica for the resolution of 2-bromo-arylacetic acid esters
  作者：David Guieysse、Georgina Sandoval、Laeticia Faure、Jean-Marc Nicaud、Pierre Monsan、Alain Marty

  DOI：10.1016/j.tetasy.2004.09.008

  日期：2004.11

  A new extracellular lipase (Lip2p) from the yeast Yarrowia lipolytica was used for the resolution of 2-bromo-arylacetic acid esters, an important class of chemical intermediates for the pharmaceutical industry. Its efficiency for the transesterification of racemic mixtures with 1-octanol in n-octane was compared with the most efficient lipases described to date, lipases from Burkholderia cepacia and Rhizomucor miehei. Resolution of 2-bromo-p-tolylacetic acid ethyl ester catalyzed by Y. lipolytica lipase showed an enantio preference of 28, almost equal to that obtained with B. cepacia lipase (E = 30). Moreover, Y lipolytica lipase presents a higher catalytic activity and an (S)-enantiopreference, while B. cepacia lipase is (R)-enantiomer selective. The most interesting result is that Y lipolytica lipase has until now been the only enzyme able to catalyze the resolution of 2-bromo-o-tolylacetic acid ethyl ester (E = 27). (C) 2004 Elsevier Ltd. All rights reserved.
• A variant of Yarrowia lipolytica lipase with improved activity and enantioselectivity for resolution of 2-bromo-arylacetic acid esters
  作者：Miguel Cancino、Philippe Bauchart、Georgina Sandoval、Jean-Marc Nicaud、Isabelle André、Valérie Dossat、Alain Marty

  DOI：10.1016/j.tetasy.2008.06.009

  日期：2008.7

  A variant of Lip2p lipase from Yarrowia lipolytica yeast was used for the resolution of 2-bromophenyl and o-tolyl acid esters, an important class of chemical intermediates for the pharmaceutical industry. In comparison with wild-type Lip2p, this variant, which contains one single amino acid change in the active site of the enzyme, V232A, displayed an enantioselectivity enhanced by one order of magnitude for the resolution of 2-bromo-phenylacetic acid ethyl ester (E-value increased from 5.5 to 59 for wild-type and V232A, respectively) and by fourfold for the resolution of 2-bromo-o-tolylacetic acid ethyl ester (going from an E-value of 27 to 111 for the wild-type and V232A, respectively). A remarkable increase in reaction velocity was also observed for both compounds, as a result of a significant gain in reactivity towards the favoured (S)-enantiomer (3- and 16-fold increase for 2-bromo-phenylacetic and -o-tolylacetic acid ethyl esters, respectively). These results demonstrate the key role of the V232 amino acid in enantiomer recognition and selectivity. (C) 2008 Elsevier Ltd. All rights reserved.