3-acetamidopropanal | 73323-68-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-acetamidopropanal
• 英文别名: N-(3-oxopropyl)acetamide
• CAS: 73323-68-9
• 化学式: C₅H₉NO₂
• mdl: MFCD11610824
• 分子量: 115.132
• InChiKey: ARJPPNFIEQKVBB-UHFFFAOYSA-N

物化性质

• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-acetamidopropanal 在 sodium tetrahydroborate 、 氢气 作用下， 以 二氯甲烷 为溶剂， 生成 N¹-acetylspermidine dihydrochloride
  参考文献：
  名称：

  Boukouvalas, John; Golding, Bernard T.; McCabe, Richard W., Angewandte Chemie, 1983, vol. 95, # 8, p. 646 - 647

  摘要：

  DOI：
• 作为产物：
  描述：

  N-(3,3-二乙氧基丙基)-乙酰胺 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.5h， 生成 3-acetamidopropanal
  参考文献：
  名称：

  Kalisiak, Jarostaw; Trauger, Sunia A.; Kalisiak, Ewa, Journal of the American Chemical Society, 2009, vol. 131, p. 378 - 386

  摘要：

  DOI：

文献信息

• Highly Regio- and Enantioselective Hydroformylation of Vinyl Esters Using Bidentate Phosphine,P-Chiral Phosphorodiamidite Ligands
  作者：Christian Schmitz、Katharina Holthusen、Walter Leitner、Giancarlo Franciò

  DOI：10.1021/acscatal.5b02846

  日期：2016.3.4

  Very high enantioselectivities of up to 97% ee accompanied by excellent regioselectivities (up to b/l > 1000) were obtained using the BettiPhos ligand (SC,SC,RP,SC)-4b bearing an additional chiral group at the aniline nitrogen. The catalyst resting state [RhH(CO)2(SC,SC,RP,SC)-4b}] was investigated by high pressure-NMR studies, revealing an equatorial–apical coordination of the bidentate ligand where

  已经制备了基于手性贝蒂碱骨架和二苯基膦基苯胺衍生物的混合二齿膦-亚磷酰胺基配体（BettiPhos）。配体在亚磷酰胺基部分具有立体异构的P原子，其构型可在很大程度上由合成途径以及碱和溶剂的选择控制。新的配体用于乙烯基酯和乙烯基酰胺的铑催化的不对称加氢甲酰化（AHF）。使用BettiPhos配体（S C，S C，R P，S C）-4b获得了高达97％ee的极高对映选择性和极佳的区域选择性（高达b / l> 1000）在苯胺氮上带有一个额外的手性基团。通过高压NMR研究了催化剂的静止状态[RhH（CO）2 （S C，S C，R P，S C）-4b }]，揭示了双齿配体的赤道-顶峰配位，其中两个磷供体通过中间体与仅通过膦基结合的配体快速交换位置。
• Mechanistic and Structural Analyses of the Roles of Active Site Residues in Yeast Polyamine Oxidase Fms1: Characterization of the N195A and D94N Enzymes
  作者：Mariya S. Adachi、Alexander B. Taylor、P. John Hart、Paul F. Fitzpatrick

  DOI：10.1021/bi3011434

  日期：2012.10.30

  mammalian polyamine and spermine oxidases. The active site of Fms1 contains three amino acid residues positioned to interact with the polyamine substrate, His67, Asn195, and Asp94. These three residues form a hydrogen-bonding triad with Asn195 being the central residue. Previous studies of the effects of mutating His67 are consistent with that residue being important both for interacting with the substrate

  来自酿酒酵母的黄素蛋白 Fms1催化泛酸生物合成途径中精胺的氧化。同样的反应由哺乳动物多胺和精胺氧化酶催化。Fms1 的活性位点包含三个氨基酸残基，可与多胺底物 His67、Asn195 和 Asp94 相互作用。这三个残基形成一个氢键三联体，其中 Asn195 是中心残基。先前对 His67 突变影响的研究与该残基对于与底物相互作用和维持三联体中的氢键都很重要 [Adachi, MS, Taylor, AB, Hart, PJ, and Fitzpatrick, PF (2012)生物化学 51, 4888–4897]。N195A 和 D94N 酶现在已被表征以评估它们在催化中的作用。两种突变主要影响还原性半反应。以N 1 -乙酰精胺作为底物，两种突变的黄素还原速率常数都降低了约 450 倍；以精胺为底物的影响较小，为 20-40 倍。N 1 -乙酰精胺的k cat / K胺- 和k cat
• Heterologous Expression and Biochemical Characterization of a Polyamine Oxidase from Arabidopsis Involved in Polyamine Back Conversion
  作者：Paraskevi Tavladoraki、Marianna Nicoletta Rossi、Giuseppe Saccuti、Miguel Angel Perez-Amador、Fabio Polticelli、Riccardo Angelini、Rodolfo Federico

  DOI：10.1104/pp.106.080911

  日期：2006.8.1

  Polyamine oxidase (PAO) is a flavin adenine dinucleotide-dependent enzyme involved in polyamine catabolism. Animal PAOs oxidize spermine (Spm), spermidine (Spd), and/or their acetyl derivatives to produce H2O2, an aminoaldehyde, and Spd or putrescine, respectively, thus being involved in a polyamine back-conversion pathway. On the contrary, plant PAOs that have been characterized to date oxidize Spm and Spd to produce 1,3-diaminopropane, H2O2, and an aminoaldehyde and are therefore involved in the terminal catabolism of polyamines. A database search within the Arabidopsis (Arabidopsis thaliana) genome sequence showed the presence of a gene (AtPAO1) encoding for a putative PAO with 45% amino acid sequence identity with maize (Zea mays) PAO. The AtPAO1 cDNA was isolated and cloned in a vector for heterologous expression in Escherichia coli. The recombinant protein was purified by affinity chromatography on guazatine-Sepharose 4B and was shown to be a flavoprotein able to oxidize Spm, norspermine, and N1-acetylspermine with a pH optimum at 8.0. Analysis of the reaction products showed that AtPAO1 produces Spd from Spm and norspermidine from norspermine, demonstrating a substrate oxidation mode similar to that of animal PAOs. To our knowledge, AtPAO1 is the first plant PAO reported to be involved in a polyamine back-conversion pathway.

  多胺氧化酶（PAO）是一种依赖于黄素腺嘌呤二核苷酸的酶，参与多胺降解。动物PAOs氧化精胺（Spm）、亚精胺（Spd）和/或它们的乙酰衍生物，产生H2O2、氨基醛和Spd或腐胺，因此参与多胺回转途径。相反，到目前为止已经表征的植物PAOs氧化Spm和Spd，产生1,3-二氨基丙烷、H2O2和氨基醛，因此参与多胺的末端降解。在拟南芥（拟南芥）基因组序列中进行数据库搜索，显示存在一个编码推测PAO的基因（AtPAO1），其氨基酸序列同玉米（玉米）PAO具有45％的同源性。 AtPAO1 cDNA被分离并克隆到Escherichia coli的载体中进行异源表达。亲和层析在guazatine-Sepharose 4B上纯化重组蛋白，并显示为一种能够在pH 8.0下氧化Spm、norspermine和N1-acetylspermine的黄素蛋白。反应产物的分析表明，AtPAO1从Spm产生Spd，从norspermine产生norspermidine，证明其底物氧化模式类似于动物PAOs。据我们所知，AtPAO1是首个报道参与多胺回转途径的植物PAO。

• Bridging the Gap between Plant and Mammalian Polyamine Catabolism: A Novel Peroxisomal Polyamine Oxidase Responsible for a Full Back-Conversion Pathway in Arabidopsis    
  作者：Panagiotis N. Moschou、Maite Sanmartin、Athina H. Andriopoulou、Enrique Rojo、Jose J. Sanchez-Serrano、Kalliopi A. Roubelakis-Angelakis

  DOI：10.1104/pp.108.123802

  日期：2008.8.4

  In contrast to animals, where polyamine (PA) catabolism efficiently converts spermine (Spm) to putrescine (Put), plants have been considered to possess a PA catabolic pathway producing 1,3-diaminopropane, Δ  1-pyrroline, the corresponding aldehyde, and hydrogen peroxide but unable to back-convert Spm to Put. Arabidopsis (Arabidopsis thaliana) genome contains at least five putative PA oxidase (PAO) members with yet-unknown localization and physiological role(s). AtPAO1 was recently identified as an enzyme similar to the mammalian Spm oxidase, which converts Spm to spermidine (Spd). In this work, we have performed in silico analysis of the five Arabidopsis genes and have identified PAO3 (AtPAO3) as a nontypical PAO, in terms of homology, compared to other known PAOs. We have expressed the gene AtPAO3 and have purified a protein corresponding to it using the inducible heterologous expression system of Escherichia coli. AtPAO3 catalyzed the sequential conversion/oxidation of Spm to Spd, and of Spd to Put, thus exhibiting functional homology to the mammalian PAOs. The best substrate for this pathway was Spd, whereas the N  1-acetyl-derivatives of Spm and Spd were oxidized less efficiently. On the other hand, no activity was detected when diamines (agmatine, cadaverine, and Put) were used as substrates. Moreover, although AtPAO3 does not exhibit significant similarity to the other known PAOs, it is efficiently inhibited by guazatine, a potent PAO inhibitor. AtPAO3 contains a peroxisomal targeting motif at the C terminus, and it targets green fluorescence protein to peroxisomes when fused at the N terminus but not at the C terminus. These results reveal that AtPAO3 is a peroxisomal protein and that the C terminus of the protein contains the sorting information. The overall data reinforce the view that plants and mammals possess a similar PA oxidation system, concerning both the subcellular localization and the mode of its action.

  与动物不同的是，多胺（PA）在动物体内可以有效地将亚精胺（Spm）转化为腐胺（Put），但是植物被认为具有一种PA降解途径，可以产生1,3-二氨基丙烷，Δ1-吡咯烷，相应的醛和过氧化氢，但无法将Spm回转为Put。拟南芥（Arabidopsis thaliana）基因组中至少包含五个假定的PA氧化酶（PAO）成员，其定位和生理作用尚未知晓。最近鉴定了AtPAO1，它是一种类似于哺乳动物Spm氧化酶的酶，可以将Spm转化为亚精胺（Spd）。在这项工作中，我们进行了对五个拟南芥基因的计算机分析，并确定PAO3（AtPAO3）是一种非典型的PAO，与其他已知的PAO相比，其同源性不高。我们表达了AtPAO3基因，并利用大肠杆菌的诱导异源表达系统纯化了相应的蛋白质。AtPAO3催化了Spm到Spd的顺序转化/氧化，以及Spd到Put的转化，因此表现出与哺乳动物PAO的功能同源性。该途径的最佳底物是Spd，而Spm和Spd的N1-乙酰衍生物的氧化效率较低。另一方面，当使用二胺（agmatine，cadaverine和Put）作为底物时，没有检测到活性。此外，虽然AtPAO3与其他已知的PAO没有显著的相似性，但它被强效的PAO抑制剂guazatine有效地抑制。AtPAO3在C端具有过氧化物酶体定位信号，当与N端融合时可以将绿色荧光蛋白定位到过氧化物酶体，但与C端融合时不能。这些结果揭示了AtPAO3是一种过氧化物酶体蛋白质，并且蛋白质的C端包含了排序信息。总体数据加强了植物和哺乳动物具有相似的PA氧化系统的观点，涉及到亚细胞定位和其作用方式。

• Genomic identification and biochemical characterization of the mammalian polyamine oxidase involved in polyamine back-conversion
  作者：Slavoljub VUJCIC、Ping LIANG、Paula DIEGELMAN、Debora L. KRAMER、Carl W. PORTER

  DOI：10.1042/bj20021779

  日期：2003.2.15

  In the polyamine back-conversion pathway, spermine and spermidine are first acetylated by spermidine/spermine N1-acetyltransferase (SSAT) and then oxidized by polyamine oxidase (PAO) to produce spermidine and putrescine respectively. Although PAO was first purified more than two decades ago, the protein has not yet been linked to genomic sequences. In the present study, we apply a BLAST search strategy to identify novel oxidase sequences located on human chromosome 10 and mouse chromosome 7. Homologous mammalian cDNAs derived from human brain and mouse mammary tumour were deduced to encode proteins of approx. 55kDa having 82% sequence identity. When either cDNA was transiently transfected into HEK-293 cells, intracellular spermine pools decreased by approx. 30%, whereas spermidine increased 2—4-fold. Lysates of human PAO cDNA-transfected HEK-293 cells, but not vector-transfected cells, rapidly oxidized N1-acetylspermine to spermidine. Substrate specificity determinations with the lysate assay revealed a preference ranking of N1-acetylspermine = N1-acetylspermidine>N1,N12-diacetylspermine>spermine; spermidine was not acted upon. This ranking is identical to that reported for purified PAO and distinctly different from the recently identified spermine oxidase (SMO), which prefers spermine over N1-acetylspermine. Monoethyl- and diethylspermine analogues also served as substrates for PAO, and were internally cleaved adjacent to a secondary amine. We deduce that the present oxidase sequences are those of the FAD-dependent PAO involved in the polyamine back-conversion pathway. In Northern blot analysis, PAO mRNA was much less abundant in HEK-293 cells than SMO or SSAT mRNA, and all three were differentially induced in a similar manner by selected polyamine analogues. The identification of PAO sequences, together with the recently identified SMO sequences, provides new opportunities for understanding the dynamics of polyamine homoeostasis and for interpreting metabolic and cellular responses to clinically-relevant polyamine analogues and inhibitors.

  在多胺反向转化途径中，精胺和亚精胺首先被亚精胺/精胺 N1-乙酰转移酶（SSAT）乙酰化，然后被多胺氧化酶（PAO）氧化，分别生成亚精胺和腐胺。虽然 PAO 早在二十多年前就被首次纯化，但该蛋白尚未与基因组序列建立联系。在本研究中，我们采用 BLAST 搜索策略，确定了位于人类第 10 号染色体和小鼠第 7 号染色体上的新型氧化酶序列。我们推导出了来自人脑和小鼠乳腺肿瘤的同源哺乳动物 cDNA，它们编码的蛋白约为 55kDa，序列同一性为 82%。将其中一种 cDNA 瞬时转染 HEK-293 细胞后，细胞内精胺池减少约 30%，而亚精胺增加 2-4 倍。转染了人 PAO cDNA 的 HEK-293 细胞的裂解液能迅速将 N1-乙酰精胺氧化为亚精胺，而转染了载体的细胞则不能。用裂解物检测法确定底物特异性的结果显示，N1-乙酰精胺=N1-乙酰精胺>N1,N12-二乙酰精胺>亚精胺；亚精胺不起作用。这种排序与报告的纯化 PAO 相同，与最近发现的精胺氧化酶（SMO）明显不同，后者更喜欢精胺而不是 N1-乙酰精胺。单乙基和二乙基精胺类似物也可作为 PAO 的底物，并在邻近仲胺的位置发生内部裂解。我们推断，目前的氧化酶序列是参与多胺反向转化途径的依赖 FAD 的 PAO 的序列。在 Northern 印迹分析中，与 SMO 或 SSAT mRNA 相比，PAO mRNA 在 HEK-293 细胞中的含量要低得多。PAO 序列的鉴定以及最近鉴定出的 SMO 序列为了解多胺平衡动态以及解释代谢和细胞对临床相关多胺类似物和抑制剂的反应提供了新的机会。