4,5-二氢-3H-吡咯-2-羧酸 | 2139-03-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 中文名称: 4,5-二氢-3H-吡咯-2-羧酸
• 中文别名: 3,4-二氢基吡咯-5-羧酸
• 英文名称: Δ¹-pyrroline-2-carboxylic acid
• 英文别名: 1-pyrroline-2-carboxylic acid；1-Pyrrolin-2-carbonsaeure；4,5-dihydro-3H-pyrrole-2-carboxylic acid；4,5-Dihydro-3H-pyrrol-2-carbonsaeure；Δ1-Pyrrolin-carbonsaeure-(2)；Δ1-Pyrrolin-2-carbonsaeure；3,4-Dihydro-2H-pyrrole-5-carboxylic acid
• CAS: 2139-03-9
• 化学式: C₅H₇NO₂
• mdl: MFCD18449543
• 分子量: 113.116
• InChiKey: RHTAIKJZSXNELN-UHFFFAOYSA-N

物化性质

• 沸点：
  255.5±23.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  49.7
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

制备方法与用途

吡咯烷-5-羧酸是一种PROTAC连接子，属于烷基/醚类。它可以用于合成PROTAC分子。

反应信息

• 作为反应物：
  描述：

  4,5-二氢-3H-吡咯-2-羧酸 在 还原型辅酶II(NADPH)四钠盐 作用下， 生成 L-prolinate ion 、 alkaline earth salt of/the/ methylsulfuric acid
  参考文献：
  名称：

  Deuterium isotope effects for the nonenzymic and glutamate dehydrogenase catalyzed reduction of an .alpha.-imino acid by NADH

  摘要：

  DOI：

  10.1021/ja00300a038
• 作为产物：
  描述：

  D-鸟氨酸 在 porcine kidney D-amino acid oxidase 作用下， 以 various solvent(s) 为溶剂， 生成 4,5-二氢-3H-吡咯-2-羧酸
  参考文献：
  名称：

  Enzymatic synthesis of cyclic amino acids by N-methyl-l-amino acid dehydrogenase from Pseudomonas putida

  摘要：

  A new enzymatic system for the synthesis of enantiomerically pure cyclic amino acids (CAA) from the corresponding diamino acids or racemic CAA is described. alpha,omega-Diamino acids were oxidized to alpha-keto acids with amino acid oxidases (AAO). The alpha-keto acids were spontaneously transformed into cyclic imino acids in the reaction medium. The resulting imines were reduced to the L-form CAA with N-methyl-L-amino acid dehydrogenase (NMAADH) from Pseudomonas putida ATCC12633 using NADPH as a cofactor. L-Form CAA were also obtained from racemic CAA using D-amino-acid oxidase and NMAADH. Using this method, a new compound [1,4]thiazepane-3-carboxylic acid (Fig. 1) was synthesized from aminopropylcystein. (c) 2006 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetasy.2006.07.005

文献信息

• Characterization of three novel enzymes with imine reductase activity
  作者：M. Gand、H. Müller、R. Wardenga、M. Höhne

  DOI：10.1016/j.molcatb.2014.09.017

  日期：2014.12

  Imine reductases (IRED) are promising catalysts for the synthesis of optically pure secondary cyclic amines. Three novel IREDs from Paenibacillus elgii B69, Streptomyces ipomoeae 91-03 and Pseudomonas putida KT2440 were identified by amino acid or structural similarity search, cloned and recombinantly expressed in E. coli and their substrate scope was investigated. Besides the acceptance of cyclic

  亚胺还原酶（IRED）是用于合成光学纯仲环胺的有前途的催化剂。通过氨基酸或结构相似性鉴定，鉴定了三种来自埃希氏Paenibacillus elgii B69，链霉菌91-03和恶臭假单胞菌KT2440的新型IRED，在大肠杆菌中克隆和重组表达，并研究了其底物范围。除了可以接受环胺外，无环胺还可以被确定为所有IRED的底物。对于恶臭假单胞菌的IRED，数据库中提供了晶体结构（PDB代码3L6D），但迄今为止尚未研究蛋白质的功能。该酶表现出最高的表观E这项研究中所研究的IRED的 （R）-甲基吡咯烷的大约E app = 52的值。因此，在24小时后使用静息细胞进行的生物催化反应中，对映体的纯度> 99％，转化率达到97％。有趣的是，可以通过诱变将组氨酸残基确认为催化残基，但是与卡那链霉菌IRED的催化Asp187的形式上已知的位置相比，该残基被放置了一圈。
• Identification and characterization of<i>trans</i>-3-hydroxy-<scp>l</scp>-proline dehydratase and Δ¹-pyrroline-2-carboxylate reductase involved in<i>trans</i>-3-hydroxy-<scp>l</scp>-proline metabolism of bacteria
  作者：Seiya Watanabe、Yoshiaki Tanimoto、Seiji Yamauchi、Yuzuru Tozawa、Shigeki Sawayama、Yasuo Watanabe

  DOI：10.1016/j.fob.2014.02.010

  日期：2014.1.1

  trans‐4‐Hydroxy‐l‐proline (T4LHyp) and trans‐3‐hydroxy‐l‐proline (T3LHyp) occur mainly in collagen. A few bacteria can convert T4LHyp to α‐ketoglutarate, and we previously revealed a hypothetical pathway consisting of four enzymes at the molecular level (J Biol Chem (2007) 282, 6685–6695; J Biol Chem (2012) 287, 32674–32688). Here, we first found that Azospirillum brasilense has the ability to grow not only on T4LHyp but also T3LHyp as a sole carbon source. In A. brasilense cells, T3LHyp dehydratase and NAD(P)H‐dependent Δ1‐pyrroline‐2‐carboxylate (Pyr2C) reductase activities were induced by T3LHyp (and d‐proline and d‐lysine) but not T4LHyp, and no effect of T3LHyp was observed on the expression of T4LHyp metabolizing enzymes: a hypothetical pathway of T3LHyp → Pyr2C → l‐proline was proposed. Bacterial T3LHyp dehydratase, encoded to LhpH gene, was homologous with the mammalian enzyme. On the other hand, Pyr2C reductase encoded to LhpI gene was a novel member of ornithine cyclodeaminase/μ‐crystallin superfamily, differing from known bacterial protein. Furthermore, the LhpI enzymes of A. brasilense and another bacterium showed several different properties, including substrate and coenzyme specificities. T3LHyp was converted to proline by the purified LhpH and LhpI proteins. Furthermore, disruption of LhpI gene from A. brasilense led to loss of growth on T3LHyp, d‐proline and d‐lysine, indicating that this gene has dual metabolic functions as a reductase for Pyr2C and Δ1‐piperidine‐2‐carboxylate in these pathways, and that the T3LHyp pathway is not linked to T4LHyp and l‐proline metabolism.

  反式-4-羟基-L-脯氨酸（T4LHyp）和反式-3-羟基-L-脯氨酸（T3LHyp）主要存在于胶原蛋白中。少数细菌能够将T4LHyp转化为α-酮戊二酸，我们之前揭示了一个由四个酶组成的分子水平的假想途径（《J Biol Chem》（2007）282，6685–6695；《J Biol Chem》（2012）287，32674–32688）。在这里，我们首先发现A. brasilense不仅可以利用T4LHyp，还可以利用T3LHyp作为唯一碳源生长。在A. brasilense细胞中，T3LHyp脱水酶和NAD(P)H依赖的Δ¹-吡咯-2-羧酸（Pyr2C）还原酶活性是由T3LHyp（以及D-脯氨酸和D-赖氨酸）诱导的，而不是由T4LHyp诱导的，并且T3LHyp对T4LHyp代谢酶的表达没有影响。提出了一条T3LHyp→Pyr2C→L-脯氨酸的假想途径。细菌T3LHyp脱水酶，由LhpH基因编码，与哺乳动物的酶同源。另一方面，由LhpI基因编码的Pyr2C还原酶是色氨酸环水解酶/μ-晶体蛋白超家族的新成员，与已知的细菌蛋白不同。此外，A. brasilense和其他细菌的LhpI酶显示出几种不同的特性，包括底物和辅酶特异性。T3LHyp通过纯化的LhpH和LhpI蛋白转化为脯氨酸。此外，破坏A. brasilense中的LhpI基因导致无法在T3LHyp、D-脯氨酸和D-赖氨酸上生长，表明该基因在这些途径中作为Pyr2C和Δ¹-哌啶-2-羧酸的还原酶具有双重代谢功能，并且T3LHyp途径不与T4LHyp和L-脯氨酸代谢相关联。
• Identification of a Human trans-3-Hydroxy-l-proline Dehydratase, the First Characterized Member of a Novel Family of Proline Racemase-like Enzymes
  作者：Wouter F. Visser、Nanda M. Verhoeven-Duif、Tom J. de Koning

  DOI：10.1074/jbc.m112.363218

  日期：2012.6

  enzyme that acts on trans-3-hydroxy-L-proline. Interestingly, a mutant enzyme in which the threonine in the active site is mutated back into cysteine regained 3-hydroxyproline epimerase activity. This result suggests that the enzymatic activity of these enzymes is dictated by a single residue. Presumably, human C14orf149 serves to degrade trans-3-hydroxy-L-proline from the diet and originating from

  最近鉴定了真核脯氨酸消旋酶样基因家族。该家族的几个成员已经被很好地表征并且已知催化游离脯氨酸或反式-4-羟脯氨酸的外消旋化。然而，大多数真核脯氨酸消旋酶样蛋白质，包括称为 C14orf149 的人类蛋白质，缺乏已知对消旋酶活性至关重要的特定半胱氨酸残基。相反，这些蛋白质总是在这个位置含有苏氨酸残基。直到现在，这些酶的功能仍未得到解决。在这项研究中，我们证明了这种类型的三种酶，包括人类 C14orf149，催化反式-3-羟基-L-脯氨酸脱水为 Delta(1)-pyrroline-2-carboxylate (Pyr2C)。这些是脯氨酸消旋酶样基因亚类的第一个酶，其酶活性已得到解决。C14orf149 也是第一种作用于反式-3-羟基-L-脯氨酸的人类酶。有趣的是，活性位点中的苏氨酸突变回半胱氨酸的突变酶重新获得了 3-羟脯氨酸差向异构酶活性。该结果表明这些酶的酶活性由单个残基决定。据推测，人类
• Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks
  作者：Suwen Zhao、Ayano Sakai、Xinshuai Zhang、Matthew W Vetting、Ritesh Kumar、Brandan Hillerich、Brian San Francisco、Jose Solbiati、Adam Steves、Shoshana Brown、Eyal Akiva、Alan Barber、Ronald D Seidel、Patricia C Babbitt、Steven C Almo、John A Gerlt、Matthew P Jacobson

  DOI：10.7554/elife.03275

  日期：——

  Metabolic pathways in eubacteria and archaea often are encoded by operons and/or gene clusters (genome neighborhoods) that provide important clues for assignment of both enzyme functions and metabolic pathways. We describe a bioinformatic approach (genome neighborhood network; GNN) that enables large scale prediction of the in vitro enzymatic activities and in vivo physiological functions (metabolic pathways) of uncharacterized enzymes in protein families. We demonstrate the utility of the GNN approach by predicting in vitro activities and in vivo functions in the proline racemase superfamily (PRS; InterPro IPR008794). The predictions were verified by measuring in vitro activities for 51 proteins in 12 families in the PRS that represent ~85% of the sequences; in vitro activities of pathway enzymes, carbon/nitrogen source phenotypes, and/or transcriptomic studies confirmed the predicted pathways. The synergistic use of sequence similarity networks3 and GNNs will facilitate the discovery of the components of novel, uncharacterized metabolic pathways in sequenced genomes.

  真细菌和古细菌的代谢途径通常由操作子和/或基因簇（基因组邻域）编码，这为确定酶功能和代谢途径提供了重要线索。我们介绍了一种生物信息学方法（基因组邻域网络；GNN），它可以大规模预测蛋白质家族中未表征酶的体外酶活性和体内生理功能（代谢途径）。我们通过预测脯氨酸消旋酶超家族（PRS；InterPro IPR008794）的体外活性和体内功能，证明了 GNN 方法的实用性。通过测量脯氨酸消旋酶超家族中约占 85% 序列的 12 个家族 51 个蛋白质的体外活性验证了预测结果；途径酶的体外活性、碳/氮源表型和/或转录组研究证实了预测的途径。序列相似性网络3 和 GNN 的协同使用将有助于发现测序基因组中未表征的新型代谢途径的组成成分。
• delta1-piperideine-2-carboxylate reductase of Pseudomonas putida
  作者：C W Payton、Y F Chang

  DOI：10.1128/jb.149.3.864-871.1982

  日期：1982.3

  Pseudomonas putida metabolizes D-lysine to delta 1-piperideine-2-carboxylate and L-pipecolate. The second step of this catabolic pathway is catalyzed by delta 1-piperideine-2-carboxylate reductase. This enzyme was isolated and purified from cells grown on DL-lysine as substrate. The enzyme was very unstable, resulting in low recovery of activity and low purity after a six-step purification procedure. The enzyme had a pH optimum of 8.0 to 8.3. The Km values for delta 1-piperideine-2-carboxylate and NADPH were 0.23 and 0.13 mM, respectively. NADPH at concentrations above 0.15 mM was inhibitory to the enzyme. Delta 1-pyrroline-5-carboxylate, pyroglutamate, and NADH were poor substrates or coenzyme for delta 1-piperideine-2-carboxylate reductase. The enzyme reaction from delta 1-piperideine-2-carboxylate to L-pipecolate was irreversible. EDTA, sodium pyrophosphate, and dithiothreitol at concentrations of 1 mM protected the enzyme during storage. The enzyme was inhibited almost totally by Zn2+, Mn2+, Hg2+ Co2+, and p-chloromercuribenzoate at concentrations of 0.1 mM. The enzyme had a molecular weight of about 200,000. Both D-lysine and L-lysine were good inducers for the enzyme. Neither delta1-piperideine-2-carboxylate nor L-pipecolate was an effective inducer for the enzyme. P. putida cells grew on D-lysine only after a 5- to 8-h lag, which could be abolished by adding a supplement of 0.01% alpha-ketoglutarate or other readily metabolizable compounds. Such a supplement also converted the noncoordinate induction of this enzyme and pipecolate oxidase, both of the D-lysine pathway, to coordinacy. However, this effect was not observed if the enzyme pair was from different pathways of lysine metabolism in this organism (i.e., the D- and L-lysine pathways).

  假单胞菌可将D-赖氨酸代谢为Δ1-哌嗪-2-羧酸和L-皮克酸。该分解途径的第二步由Δ1-哌嗪-2-羧酸还原酶催化。该酶从以DL-赖氨酸为底物的细胞中分离和纯化。该酶非常不稳定，经过六步纯化过程后，活性和纯度都很低。该酶的pH最适值为8.0至8.3。Δ1-哌嗪-2-羧酸和NADPH的Km值分别为0.23和0.13 mM。浓度高于0.15 mM的NADPH对酶有抑制作用。Δ1-吡咯烷-5-羧酸、吡二酸和NADH都是Δ1-哌嗪-2-羧酸还原酶的较差底物或辅酶。从Δ1-哌嗪-2-羧酸到L-皮克酸的酶反应是不可逆的。1 mM的EDTA、焦磷酸二钠和二硫苏糖醇可保护酶在储存过程中。0.1 mM的Zn2+、Mn2+、Hg2+、Co2+和对氯汞苯甲酸酯几乎完全抑制了该酶。该酶的分子量约为200,000。D-赖氨酸和L-赖氨酸均是该酶的良好诱导剂。Δ1-哌嗪-2-羧酸和L-皮克酸都不是该酶的有效诱导剂。假单胞菌细胞在D-赖氨酸上生长需要5至8小时的滞后期，此时加入0.01%的α-酮戊二酸或其他易于代谢的化合物可消除滞后期。这种补充剂还将该酶和D-赖氨酸途径的皮克酸氧化酶的非配合诱导转化为配合诱导。但如果该酶对来自该生物体的赖氨酸代谢不同途径（即D-和L-赖氨酸途径）的酶对，则不会观察到这种效应。