4-carboxybenzyl trans-1,3-butadiene-1-carbamate | 165814-48-2

• 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: 4-carboxybenzyl trans-1,3-butadiene-1-carbamate
• 英文别名: 4-carboxybenzyl-trans-1,3-butadiene-1-carbamate；4-[[(1E)-buta-1,3-dienyl]carbamoyloxymethyl]benzoic acid
• CAS: 165814-48-2
• 化学式: C₁₃H₁₃NO₄
• 分子量: 247.251
• InChiKey: HGMJQUSLRHRARW-FPYGCLRLSA-N

物化性质

• 沸点：
  429.7±45.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-二甲基丙烯酰胺 、 4-carboxybenzyl trans-1,3-butadiene-1-carbamate 在 qa. phosphate-buffered saline 作用下， 生成 4-[[6-(Dimethylcarbamoyl)cyclohex-2-en-1-yl]carbamoyloxymethyl]benzoic acid
  参考文献：
  名称：

  Experimental Determination of the Absolute Enantioselectivity of an Antibody-Catalyzed Diels−Alder Reaction and Theoretical Explorations of the Origins of Stereoselectivity

  摘要：

  The exo and endo Diels-Alder adducts of p-methoxycarbonylbenzyl trans-1,3-butadiene- 1 carbamate and N,N-dimethylacrylamide have been synthesized, and the absolute configurations of resolved enantiomers have been determined. On the basis of this information, the absolute enantioselectivities of the Diels-Alder reaction catalyzed by antibodies 13G5 and 4D5 as well as other catalytic antibodies elicited in the same immunizations have been established. The effects of different arrangements of catalytic residues on the structure and energetics of the possible Diels-Alder transition states were modeled quantum mechanically at the B3LYP/6-311++G**//B3LYP/6-31+G** level of theory. Flexible docking of these enantiomeric transition states in the antibody active site followed by molecular dynamics on the resulting complexes provided a prediction of the transition-state binding modes and an explanation of the origin of the observed enantioselectivity of antibody 13G5.

  DOI：

  10.1021/ja020879d
• 作为产物：
  描述：

  4-(methoxycarbonyl)benzyl trans-1,3-butadiene-1-carbamate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 9.0h， 以95%的产率得到4-carboxybenzyl trans-1,3-butadiene-1-carbamate
  参考文献：
  名称：

  Experimental Determination of the Absolute Enantioselectivity of an Antibody-Catalyzed Diels−Alder Reaction and Theoretical Explorations of the Origins of Stereoselectivity

  摘要：

  The exo and endo Diels-Alder adducts of p-methoxycarbonylbenzyl trans-1,3-butadiene- 1 carbamate and N,N-dimethylacrylamide have been synthesized, and the absolute configurations of resolved enantiomers have been determined. On the basis of this information, the absolute enantioselectivities of the Diels-Alder reaction catalyzed by antibodies 13G5 and 4D5 as well as other catalytic antibodies elicited in the same immunizations have been established. The effects of different arrangements of catalytic residues on the structure and energetics of the possible Diels-Alder transition states were modeled quantum mechanically at the B3LYP/6-311++G**//B3LYP/6-31+G** level of theory. Flexible docking of these enantiomeric transition states in the antibody active site followed by molecular dynamics on the resulting complexes provided a prediction of the transition-state binding modes and an explanation of the origin of the observed enantioselectivity of antibody 13G5.

  DOI：

  10.1021/ja020879d

文献信息

• Impact of scaffold rigidity on the design and evolution of an artificial Diels-Alderase
  作者：Nathalie Preiswerk、Tobias Beck、Jessica D. Schulz、Peter Milovník、Clemens Mayer、Justin B. Siegel、David Baker、Donald Hilvert

  DOI：10.1073/pnas.1401073111

  日期：2014.6.3

  Creating artificial enzymes that catalyze arbitrary chemical reactions is challenging. Although computational approaches to this problem hold great promise, starting designs typically exhibit low efficiency and require extensive optimization through directed evolution. In this study, we chronicle the evolution of a modestly active, computationally designed Diels-Alderase into a proficient biocatalyst for an abiological [4+2] cycloaddition reaction. Biochemical and structural characterization of the evolved enzyme reveals the molecular origins of its enhanced efficiency. The close match between the experimental structure, which changed only subtly over the course of evolution, and the original design model is particularly notable. In addition to enhancing our understanding of the principles of enzymatic catalysis, these findings should aid future efforts to produce active enzymes more reliably.

  创造能够催化任意化学反应的人工酶是具有挑战性的。虽然计算方法在解决这个问题上具有巨大的潜力，但起始设计通常表现出低效率，并需要通过定向进化进行广泛优化。在这项研究中，我们记录了一个适度活跃的、计算设计的Diels-Alderase酶的进化过程，将其转化为对非生物[4+2]环加成反应具有高效催化作用的生物催化剂。对进化酶的生化和结构特征的表征揭示了其增强效率的分子起源。实验结构与原始设计模型之间的密切匹配尤其值得注意，因为在进化过程中，实验结构只发生了微小的变化。除了增强我们对酶催化原理的理解外，这些发现还应该有助于未来生产更可靠的活性酶的努力。

• Anti-Metallocene Antibodies: A New Approach to Enantioselective Catalysis of the Diels-Alder Reaction
  作者：Jari T. Yli-Kauhaluoma、Jon A. Ashley、Chih-Hung Lo、Lee Tucker、Mary M. Wolfe、Kim D. Janda

  DOI：10.1021/ja00132a001

  日期：1995.7

  We have shown how a constrained bicyclo[2.2.2]octene hapten can elicit antibody catalysts for the Diels-Alder reaction between 4-carboxybenzyl trans-1,3-butadiene-1-carbamate and N,N-dimethylacrylamide (Gouverneur, V. E,; de Pascual-Teresa, B.; Beno, B.; Janda, K. D.; Lerner, R. A. Science 1993, 262, 204). In the present study we have developed a new approach to hapten design for elicitation of Diels-Alder catalytic antibodies. Our strategy was to engage the freely rotating eta(5)-cyclopentadienyl iron complex as the haptenic group. By applying such a flexible hapten we set out to determine if the immune system could freeze out a conformer which mimics the Diels-Alder transition state and hence produce new Diels-Alderases. If so, how would the catalytic rates, diastereo- and enantioselectivity of these antibodies compare with those of antibodies elicited by the former methodology? We generated antibodies that catalyzed the Diels-Alder reaction with high enantio- and diastereoselectivity and had effective molarities (EM) comparable to those of antibodies elicited using the constrained bicyclo[2.2.2]octene haptens. This methodology offers a new approach to the production of antibodies for the catalysis of other reactions with pericyclic, highly-ordered transition states.
• ENZYME CATALYSTS FOR DIELS-ALDER REACTIONS
  申请人：Baker David

  公开号：US20120100594A1

  公开（公告）日：2012-04-26

  The present invention provides enzyme catalysts for Diels-Alder reactions, including intermolecular Diels-Alder reactions, as well as protein scaffolds for making such enzyme catalysts. In other aspects, the invention provides methods of making the enzyme catalysts, including by de novo computational design. The present invention thereby provides enzyme catalysts capable of catalyzing a desired Diels-Alder reaction, including with a specified or desired stereo-selectivity.
• [EN] ENZYME CATALYSTS FOR DIELS-ALDER REACTIONS<br/>[FR] CATALYSEURS ENZYMATIQUES POUR RÉACTIONS DE DIELS-ALDER
  申请人：UNIV WASHINGTON

  公开号：WO2010077470A2

  公开（公告）日：2010-07-08

  The present invention provides enzyme catalysts for Diels-Alder reactions, including intermolecular Diels-Alder reactions, as well as protein scaffolds for making such enzyme catalysts. In other aspects, the invention provides methods of making the enzyme catalysts, including by de novo computational design. The present invention thereby provides enzyme catalysts capable of catalyzing a desired Diels-Alder reaction, including with a specified or desired stereo-selectivity.
• Experimental Determination of the Absolute Enantioselectivity of an Antibody-Catalyzed Diels−Alder Reaction and Theoretical Explorations of the Origins of Stereoselectivity
  作者：Carina E. Cannizzaro、Jon A. Ashley、K. D. Janda、K. N. Houk

  DOI：10.1021/ja020879d

  日期：2003.3.1

  The exo and endo Diels-Alder adducts of p-methoxycarbonylbenzyl trans-1,3-butadiene- 1 carbamate and N,N-dimethylacrylamide have been synthesized, and the absolute configurations of resolved enantiomers have been determined. On the basis of this information, the absolute enantioselectivities of the Diels-Alder reaction catalyzed by antibodies 13G5 and 4D5 as well as other catalytic antibodies elicited in the same immunizations have been established. The effects of different arrangements of catalytic residues on the structure and energetics of the possible Diels-Alder transition states were modeled quantum mechanically at the B3LYP/6-311++G**//B3LYP/6-31+G** level of theory. Flexible docking of these enantiomeric transition states in the antibody active site followed by molecular dynamics on the resulting complexes provided a prediction of the transition-state binding modes and an explanation of the origin of the observed enantioselectivity of antibody 13G5.