trimethylpyruvate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: trimethylpyruvate
• 英文别名: t-Butylglyoxylate；3,3-dimethyl-2-oxobutanoate
• 化学式: C₆H₉O₃
• 分子量: 129.136
• InChiKey: IAWVHZJZHDSEOC-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  trimethylpyruvate 在 2-氨基戊二酸酯 作用下， 反应 0.5h， 以100%的产率得到L-叔亮氨酸
  参考文献：
  名称：

  Asymmetric synthesis of l-tert-leucine and l-3-hydroxyadamantylglycine using branched chain aminotransferase

  摘要：

  L-Tert-leucine (Tle) and L-3-hydroxyadamantylglycine of (HAG) are important intermediates for a variety of pharmaceutical classes. They were asymmetrically produced from corresponding keto acids using branched-chain aminotransferase (SCAT) with L-glutamate (Glu) as an amino donor. For the production of L-Tle and L-HAG, BCAT from Enterobacter sp. TL3 (BCATen) and BCAT from Escherichia coli K12 (ilvE, newly named as BCATes) were used, respectively. In our current study, we characterized the basic properties of BCATen and BCATes such as substrate specificity, enantioselectivity, and kinetic parameters. The activities of BCATen and BCATes were inhibited severely by alpha-ketoglutarate which is a deaminated product of L-Glu. In the presence of 10 mM alpha-ketoglutarate, both enzymes activities were reduced up to 80%. In order to overcome product inhibition by alpha-ketoglutarate and the problem of equilibrium of the transamination reaction, coupling reactions were carried out with L-glutamate dehydrogenase (GDH)/formate dehydrogenase (FDH) and AspAT. The coupling reaction dramatically increased the yields of both target compounds. 135 mM of L-Tle (>99% ee)was produced from 150 mM corresponding keto acid in BCATen/GDH/FDH coupling reaction with 90% conversion. In addition, 90.5 mM L-HAG (>99% ee) was produced from 100 mM corresponding keto acid in BCATes/AspAT coupling reaction using recombinant whole-cells. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2010.05.014
• 作为产物：
  描述：

  L-叔亮氨酸 、 2-氧代-戊二酸离子(2-) 在 pyridoxal 5-triphosphate 、 branched-chain-amino-acid transaminase from E_. coli 作用下， 以 phosphate buffer 为溶剂， 生成 2-氨基戊二酸酯 、 trimethylpyruvate
  参考文献：
  名称：

  支链氨基酸转氨酶催化反应的热力学

  摘要：

  摘要 测量了支链氨基酸转氨酶催化反应的表观平衡常数和反应热焓。在温度 298.15 K 和 pH 范围（7.15 至 7.24）下研究了以下生化反应：l-缬氨酸（aq）+ 2-氧代戊二酸（aq）= 2-氧代异戊酸（aq）+ l-谷氨酸（aq） ;l-亮氨酸(aq) + 2-氧代戊二酸(aq) = 2-氧代异己酸(aq) + l-谷氨酸(aq); 和叔-亮氨酸(aq) + 2-氧代戊二酸(aq) = 3,3-二甲基-2-氧代丁酸(aq) + l-谷氨酸(aq)。结果已用于计算涉及特定物种的参考反应的平衡常数和标准摩尔焓 ΔrHmo、熵 ΔrSmo 和吉布斯自由能 ΔrGmochanges。还计算了这些反应在生理条件下的表观平衡常数和标准转换吉布斯自由能变化。讨论了使用这些结果优化支链氨基酸的产品产量。

  DOI：

  10.1006/jcht.2000.0686

文献信息

• 3-Benzyl-7-substituted acetamido-3-cephem-4-carboxylic acids and
  申请人：Beecham Group Limited

  公开号：US03939157A1

  公开（公告）日：1976-02-17

  Antimicrobially active ceph-3-ems having in the 3-position a benzyl or mono-halobenzyl group, preferably with the mono-halo group in the para-position of the phenyl part of the benzyl group.

  具有抗微生物活性的Ceph-3-ems，在其3位上有苯甲基或单卤苯甲基基团，最好是单卤基在苯甲基的苯环部分的对位。
• Method for preparing optically active amino acid using cosubstrate shuttling of transaminase
  申请人：INDUSTRY-ACADEMIC COOPERATION FOUNDATION, YONSEI UNIVERSITY

  公开号：US09376694B2

  公开（公告）日：2016-06-28

  The present disclosure relates to a method for preparing an optically active amino acid using cosubstrate shuttling of transaminase. The method includes coupling a reaction of converting a keto acid to an amino acid by α-transaminase and a reaction of transferring an amino group of an amine substrate by ω-transaminase (TA) using an amino acid cosubstrate. The present disclosure allows production of various optically active amino acids with high purity and high efficiency by solving the low equilibrium constant problem of transaminase and is applicable to production of various optically active amino acids in industrial scale. Since the present disclosure allows easy production of various unnatural amino acids having high reactivity and stability, which are used as pharmaceutical precursors, it can be usefully employed in preparation of pharmaceuticals, food additives and various animal feeds.

  本公开涉及一种使用共基质穿梭转氨酶制备光学活性氨基酸的方法。该方法包括使用氨基酸共基质耦合将酮酸转化为氨基酸的α-转氨酶反应和使用ω-转氨酶（TA）转移胺基底物的氨基团的反应。本公开解决了转氨酶低平衡常数问题，可以高纯度、高效率地生产各种光学活性氨基酸，并可应用于工业规模的各种光学活性氨基酸的生产。由于本公开可以轻松生产具有高反应性和稳定性的各种非天然氨基酸，这些氨基酸被用作制药前体，因此可以在制备制药、食品添加剂和各种动物饲料方面得到有用的应用。
• METHOD FOR PREPARING OPTICALLY ACTIVE AMINO ACID USING COSUBSTRATE SHUTTLING OF TRANSAMINASE
  申请人：INDUSTRY-ACADEMIC COOPERATION FOUNDATION, YONSEI UNIVERSITY

  公开号：US20150284750A1

  公开（公告）日：2015-10-08

  The present disclosure relates to a method for preparing an optically active amino acid using cosubstrate shuttling of transaminase. The method includes coupling a reaction of converting a keto acid to an amino acid by α-transaminase and a reaction of transferring an amino group of an amine substrate by ω-transaminase (TA) using an amino acid cosubstrate. The present disclosure allows production of various optically active amino acids with high purity and high efficiency by solving the low equilibrium constant problem of transaminase and is applicable to production of various optically active amino acids in industrial scale. Since the present disclosure allows easy production of various unnatural amino acids having high reactivity and stability, which are used as pharmaceutical precursors, it can be usefully employed in preparation of pharmaceuticals, food additives and various animal feeds.

  本公开涉及使用共基底穿梭转氨酶的方法制备光学活性氨基酸。该方法包括使用氨基酸共基底耦合α-转氨酶将酮酸转化为氨基酸的反应和使用ω-转氨酶（TA）转移胺基底物的胺基的反应。本公开解决了转氨酶低平衡常数问题，可高效高纯度地生产各种光学活性氨基酸，并适用于工业规模生产。由于本公开允许轻松生产具有高反应性和稳定性的各种非天然氨基酸，这些氨基酸可用作制药前体，因此可以在制备药物、食品添加剂和各种动物饲料方面得到有用的应用。
• Biocatalytic cascade reactions for asymmetric synthesis of aliphatic amino acids in a biphasic reaction system
  作者：Eul-Soo Park、Jong-Shik Shin

  DOI：10.1016/j.molcatb.2015.07.011

  日期：2015.11

  Enantiopure aliphatic amino acids, including 1-3-hydroxyadamantylglycine (L-Hag), L-tert-leucine (L-Tle) and L-norvaline, are essential chiral building blocks for a number of pharmaceutical drugs. Here, we developed cascade enzyme reactions in an extractive biphasic system using a branched-chain amino acid transaminase (BCTA) and an (S)-selective omega-transaminase (omega-TA) for asymmetric synthesis of the aliphatic amino acids from achiral alpha-keto acid precursors. The extractive cascade reactions enabled equilibrium shift of the BCTA reaction by recycling an amino acid cosubstrate as well as acceleration of the omega-TA reaction by removing an inhibitory ketone product from an aqueous phase. Starting with 20 mM alpha-keto acid, 4 mM rac-homoalanine and 50 mM rac-alpha-methylbenzylamine (rac-alpha-MBA), the biphasic cascade reactions afforded synthesis of four unnatural amino acids (i.e., L-Tle, L-Hag, L-norvaline and L-norleucine) and two natural amino acids (i.e., L-valine and L-Leucine) with >92% conversion yield and >99.9% ee. To demonstrate the industrial feasibility of the extractive cascade reaction, preparative-scale synthesis of L-Hag was performed in a reaction mixture consisting of 300 mL hexane and 50 mL aqueous solution (50 mM phosphate buffer, pH 7.0) charged with 50 mM keto acid substrate, 5 mM L-homoalanine, 120 mM rac-alpha-MBA, 2 U/mL BCTA and 16 U/mL omega-TA. Conversion yield of L-Hag reached 92% with >99.9% ee at 70 h. Product isolation led to 0.32 g white solid of L-Hag (62 % isolation yield). (C) 2015 Elsevier B.V. All rights reserved.
• Thermodynamics of reactions catalysed by branched-chain-amino-acid transaminase
  作者：Yadu B. Tewari、Robert N. Goldberg、J.David Rozzell

  DOI：10.1006/jcht.2000.0686

  日期：2000.10

  Abstract Apparent equilibrium constants and calorimetric enthalpies of reaction have been measured for reactions catalysed by branched-chain-amino-acid transaminase. The following biochemical reactions have been studied at the temperature 298.15 K and in the pH range (7.15 to 7.24):l-valine(aq) + 2-oxoglutarate(aq) = 2-oxoisovalerate(aq) + l-glutamate(aq);l-leucine(aq) + 2-oxoglutarate(aq) = 2-oxoisocaproate(aq)

  摘要 测量了支链氨基酸转氨酶催化反应的表观平衡常数和反应热焓。在温度 298.15 K 和 pH 范围（7.15 至 7.24）下研究了以下生化反应：l-缬氨酸（aq）+ 2-氧代戊二酸（aq）= 2-氧代异戊酸（aq）+ l-谷氨酸（aq） ;l-亮氨酸(aq) + 2-氧代戊二酸(aq) = 2-氧代异己酸(aq) + l-谷氨酸(aq); 和叔-亮氨酸(aq) + 2-氧代戊二酸(aq) = 3,3-二甲基-2-氧代丁酸(aq) + l-谷氨酸(aq)。结果已用于计算涉及特定物种的参考反应的平衡常数和标准摩尔焓 ΔrHmo、熵 ΔrSmo 和吉布斯自由能 ΔrGmochanges。还计算了这些反应在生理条件下的表观平衡常数和标准转换吉布斯自由能变化。讨论了使用这些结果优化支链氨基酸的产品产量。