5,6-二羟基-1,3-环己二烯-1-羧酸 | 176487-06-2

• 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
• 中文名称: 5,6-二羟基-1,3-环己二烯-1-羧酸
• 英文名称: trans-2.3-Dihydroxy-2.3-dihydro-benzoesaeure
• 英文别名: (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylic acid
• CAS: 176487-06-2
• 化学式: C₇H₈O₄
• 分子量: 156.138
• InChiKey: INCSWYKICIYAHB-WDSKDSINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,6-二羟基-1,3-环己二烯-1-羧酸 在 吡啶 、 四丁基氟化铵 、 二异丁基氢化铝 、 碳酸氢钠 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 [(1S,2R,3S,6R)-2,3-dihydroxy-7-oxabicyclo[4.1.0]hept-4-en-1-yl]methyl benzoate
  参考文献：
  名称：

  Cyclohexadiene-trans-diols as versatile starting material in natural product synthesis: short and efficient synthesis of iso-crotepoxide and ent-senepoxide

  摘要：

  本文介绍了一种以微生物生产的 (+)-trans-2,3-dihydroxy-2,3-dihydrobenzoic acid 为原料，通过 Regio- 和立体选择性环氧化作用合成 ent-senepoxide 和 iso-crotepoxide 的新方法。

  DOI：

  10.1039/b110420a
• 作为产物：
  描述：

  葡萄糖 在 air 、 Escherichia coli AN₁₉₃ H₁₈₈₂ containing genes entB 作用下， 以 various solvent(s) 为溶剂， 以73%的产率得到5,6-二羟基-1,3-环己二烯-1-羧酸
  参考文献：
  名称：

  Synthesis of Functionalized Cyclohexadiene-trans-Diols with Recombinant Cells of Escherichia coli

  摘要：

  As valuable chiral building blocks for the syntheses of natural products and pharmacologically active substances, especially of carbohydrate mimetics, functionalized cyclohexadiene-trans-diols such as (2S,3S)-dihydroxy-2,3-dihydrobenzoic acid (1) can be prepared easily in 17 % yield starting from glucose by using metabolically deregulated, recombinant microorganisms such as the Escherichia coli strain AN193.

  DOI：

  10.1002/1521-3773(20010202)40:3<555::aid-anie555>3.0.co;2-0

文献信息

• (S,S)-2,3-Dihydroxy-2,3-dihydrobenzoic Acid: Microbial Access with Engineered Cells ofEscherichia coli and Application as Starting Material in Natural-Product Synthesis
  作者：Dirk Franke、Volker Lorbach、Simon Esser、Christian Dose、Georg A. Sprenger、Markus Halfar、Jörg Thömmes、Rolf Müller、Ralf Takors、Michael Müller

  DOI：10.1002/chem.200204265

  日期：2003.9.5

  deletions in chorismate-utilising pathways towards aromatic amino acids, neither chorismate nor any other metabolic intermediates were found as by-products. Fermentation of these strains in a 30 L pH-controlled stirred tank reactor showed that 2,3-trans-CHD could be obtained in concentrations of up to 4.6 g L(-1). This demonstrates that post-chorismate metabolites are accessible on a preparative scale by using

  环己二烯-反式-5,6-二醇，如（S，S）-2,3-二羟基-2,3-二氢苯甲酸（2,3-trans-CHD）已显示出作为手性原料的重要性生物活性物质的合成，特别是石竹的合成。通过使用代谢途径工程方法，克隆了编码异麦芽糖酶和异麦酸合酶的大肠杆菌基因entB和entC，并在缺乏entA的大肠杆菌菌株中过表达，该菌株编码2，3-二羟基苯甲酸酯合酶。相应的EntB / EntC酶活性增加30倍会影响2,3-trans-CHD在培养基中的积累。尽管该菌株在利用分支酸酯的途径中没有向芳香族氨基酸的缺失，但是分支酸酯和任何其他代谢中间体均未被发现为副产物。在30 L pH受控的搅拌釜反应器中发酵这些菌株表明，可以以最高4.6 g L（-1）的浓度获得2,3-trans-CHD。这表明，通过使用代谢途径工程技术，可以在制备规模上获得准巧克力酸盐后的代谢产物。从发酵盐中分离和分离可以经济地通过阴离子交换色谱法一步完成，或者通过反应萃取进行。从2
• Biosynthetic Production of 4-Amino 4-Deoxychorismate (Adc) and [3R,4R]-4-Amino-3-Hydroxycyclohexa-1,5-Diene-1-Carboxylic Acid (3,4-Cha)
  申请人：Wubbolts Marcel Gerhardus

  公开号：US20080311631A1

  公开（公告）日：2008-12-18

  The invention relates to a process for the biosynthetic production of 4-amino-4-deoxychorismate (ADC) performed fermentatively in vivo with a 4-amino-4-deoxychorismate synthase, preferably a PabAB bipartite protein (which may be a fusion protein), at an increased level of activity, thereby obtaining a broth comprising ADC and 4-amino-4-deoxyprephenate (ADP), that are recovered. The invention also relates to a further process of converting the ADP into p-aminophenylalanine. The invention, moreover relates to biosynthetic production of [3R,4R]-4-amino-3-hydroxycyclohexa-1,5-diene-1-carboxylic acid (3,4-CHA), by concerted action of such 4-amino-4-deoxychorismate synthase and of an enzyme capable of converting isochorismate into [5S,6S]-5,6 dihydroxycyclohexa-1,3-diene-1-carboxylic acid (2,3-CHD), preferably a phenazine biosynthesis protein PhzD, including recovery of 3,4-CHA. The invention also relates to expression vectors and host cells for use in any of such processes. The invention further relates to the use of 3,4-CHA as a catalytically active product, in particular as a chiral catalyst. And the invention finally relates to synthesis of oseltamivir phosphate from 3,4-CHA.

  该发明涉及一种生物合成4-氨基-4-脱氧黄嘌呤酸（ADC）的过程，通过在体内发酵使用4-氨基-4-脱氧黄嘌呤酸合成酶，优选为PabAB二分体蛋白（可为融合蛋白）在增加的活性水平下进行，从而获得包含ADC和4-氨基-4-脱氧前苯酸（ADP）的菌液，然后进行回收。该发明还涉及将ADP转化为对氨基苯丙氨酸的进一步过程。此外，该发明还涉及通过这种4-氨基-4-脱氧黄嘌呤酸合成酶和能够将异黄嘌呤酸转化为[5S，6S]-5,6-二羟基环己基-1,3-二烯-1-羧酸（2,3-CHD）的酶的协同作用，优选为苯肼生物合成蛋白PhzD，生物合成[3R,4R]-4-氨基-3-羟基环己-1,5-二烯-1-羧酸（3,4-CHA），并回收3,4-CHA。该发明还涉及用于任何这种过程的表达载体和宿主细胞。此外，该发明还涉及将3,4-CHA用作具有催化活性的产品，特别是作为手性催化剂。最后，该发明还涉及从3,4-CHA合成奥司他韦磷酸盐的方法。
• Biosynthetic production of 4-amino-4-deoxychorismate (ADC) and [3R,4R]-4-amino-3-hydroxycyclohexa-1,5-diene-1-carboxylic acid (3,4-CHA)
  申请人：DSM IP Assets B.V.

  公开号：EP1602730A2

  公开（公告）日：2005-12-07

  The invention relates to a process for the biosynthetic production of 4-amino-4-deoxychorismate (ADC) performed fermentatively in vivo with a 4-amino-4-deoxychorismate synthase, preferably a PabAB bipartite protein (which may be a fusion protein), at an increased level of activity, thereby obtaining a broth comprising ADC and 4-amino-4-deoxyprephenate (ADP), that are recovered. The invention also relates to a further process of converting the ADP into p-aminophenylalanine. The invention, moreover relates to biosynthetic production of [3R,4R]-4-amino-3-hydroxycyclohexa-1,5-diene-1-carboxylic acid (3,4-CHA), by concerted action of such 4-amino-4-deoxychorismate synthase and of an enzyme capable of converting isochorismate into [5S,6S]-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylic acid (2,3-CHD), preferably a phenazine biosynthesis protein PhzD, including recovery of 3,4-CHA. The invention also relates to expression vectors and host cells for use in any of such processes. And the invention finally relates to synthesis of oseltamivir phosphate from 3,4-CHA.

  本发明涉及一种生物合成生产4-氨基-4-脱氧胆甾酸盐（ADC）的工艺，该工艺在体内发酵，使用活性水平提高的4-氨基-4-脱氧胆甾酸盐合成酶，最好是PabAB双蛋白（可以是融合蛋白），从而获得由ADC和4-氨基-4-脱氧苯甲酸盐（ADP）组成的肉汤，并进行回收。本发明还涉及将 ADP 转化为对氨基苯丙氨酸的进一步工艺。此外，本发明还涉及通过这种 4-氨基-4-脱氧胆甾酸合成酶和一种能将异胆甾酸转化为 [5S.6S]-5,6- 二烯-1-羧酸的酶的协同作用，生物合成生产 [3R,4R]-4-氨基-3-羟基环己-1,5-二烯-1-羧酸（3,4-CHA）、6S]-5,6-二羟基环己-1,3-二烯-1-羧酸（2,3-CHD）的酶，最好是酚嗪生物合成蛋白 PhzD，包括回收 3,4-CHA。本发明还涉及用于上述任何过程的表达载体和宿主细胞。最后，本发明还涉及从 3,4-CHA合成磷酸奥司他韦。
• Improved biosynthetic production of 2,3-trans-CHD
  申请人：DSM IP Assets B.V.

  公开号：EP1734130A1

  公开（公告）日：2006-12-20

  The invention relates to a process for the biosynthetic production of [5S,6S]-5,6-dihydroxy-cyclohexa-1,3-diene-1-carboxylic acid (2,3-trans-CHD) in an Escherichia microorganism having increased activity of isochorismate synthase and isochorismatase, and being deficient in activity of 2,3-dihydroxybenzoate synthase, wherein the process is carried out in a chorismate overproducing host microorganism also having decreased glucose dehydrogenase activity. In this improved biosynthetic process, 2,3-trans-CHD is being produced in high yields and at concentrations in the biosynthetic reaction medium of at least 12 g/l. The invention further relates to the use of the supernatant of a process for the biosynthetic production of [5S,6S]-5,6-dihydroxy-cyclohexa-1,3-diene-1-carboxylic acid (2,3-trans-CHD) where the concentration of 2,3-trans-CHD in the process has arrived at a concentration of at least 12 g/l as a source for a co-factor for PQQ dependent enzymes.

  本发明涉及一种生物合成生产[5S,6S]-5,6-二羟基-环己-1,3-二烯-1-羧酸（2,3-反式-CHD）的工艺，该工艺是在异雏菊酸合成酶和异雏菊酸酶活性增加，而 2,3-二羟基苯甲酸合成酶活性不足的埃希氏微生物中进行的、而 2,3-二羟基苯甲酸合成酶活性不足，其中该过程是在过量产生氯代苯甲酸的宿主微生物中进行的，该宿主微生物的葡萄糖脱氢酶活性也降低了。在这种改进的生物合成工艺中，2,3-反式-CHD 的产量很高，在生物合成反应介质中的浓度至少为 12 克/升。 本发明进一步涉及[5S,6S]-5,6-二羟基-环己-1,3-二烯-1-羧酸（2,3-反式-CHD）生物合成生产过程中上清液的用途，在该过程中，2,3-反式-CHD 的浓度至少达到 12 克/升，作为 PQQ 依赖酶的辅助因子来源。
• MICROORGANISM CAPABLE OF PRODUCING L-AMINO ACID, AND METHOD FOR PRODUCING L-AMINO ACID
  申请人：Ajinomoto Co., Inc.

  公开号：EP2336347A1

  公开（公告）日：2011-06-22

  An L-amino acid is produced by culturing a bacterium belonging to the family Enterobacteriaceae, which has an L-amino acid-producing ability and inherently has an activity of a glucose dehydrogenase that uses pyrroloquinoline quinone as a coenzyme, but has been modified so that the activity of the glucose dehydrogenase is reduced, in a medium to produce and accumulate the L-amino acid in culture, and collecting the L-amino acid from the culture.

  一种 L-氨基酸是通过在培养基中培养一种属于肠杆菌科的细菌来生产的，这种细菌具有生产 L-氨基酸的能力，并且本身具有以吡咯喹啉醌为辅酶的葡萄糖脱氢酶的活性，但经过改良，使葡萄糖脱氢酶的活性降低，从而在培养基中生产和积累 L-氨基酸，并从培养基中收集 L-氨基酸。