(2S,3R)-2-Amino-3-hydroxy-4-(4-nitrophenyl)butanoic acid | 99268-38-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3R)-2-Amino-3-hydroxy-4-(4-nitrophenyl)butanoic acid
• 英文别名: 4-(4-nitrophenyl)-L-threonine
• CAS: 99268-38-9
• 化学式: C₁₀H₁₂N₂O₅
• 分子量: 240.216
• InChiKey: HUGPLGZGZBFEOQ-BDAKNGLRSA-N

物化性质

• 沸点：
  512.8±50.0 °C(Predicted)
• 密度：
  1.467±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,3R)-2-Amino-3-hydroxy-4-(4-nitrophenyl)butanoic acid 在 吡啶 、 sodium hydroxide 、 4-溴苯磺酰氯 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.33h， 生成 (3S,4R)-3-<<(2-Nitrophenyl)sulfenyl>amino>-4-<(4-nitrophenyl)methyl>-2-oxetanone
  参考文献：
  名称：

  Synthesis, Stability, and Antimicrobial Activity of (+)-Obafluorin and Related .beta.-Lactone Antibiotics

  摘要：

  Optically pure obafluorin(l), an antibacterial agent from Pseudomonas fluorescens, was synthesized in six steps via lactonization of N-[(2-nitrophenyl)sulfenyl]-(2S,3R)-2-amino-3-hydroxy-4-(4-nitrophenyl)butanoic acid (12a), which was prepared in a stereospecific manner from 4-nitrophenylacetaldehyde (9a) and (S)-1-benzoyl-2-tert-butyl-3-methyl-4-imidazolidinone (7). A series of analogues was then synthesized in order to probe structural features required for antibacterial activity as well as those responsible for the hydrolytic decomposition of 1 to the corresponding hydroxy acid 23a. Analogues 22b and 22e wherein the nitro group of 1 is replaced with hydrogen and chlorine, respectively, were prepared in a fashion similar to 1, as were the N-acetyl, N-benzoyl, and N-2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetyl (ATMO) derivatives 24a-c. The tosylate salt of L-threonine-beta-lactone (21) was transformed to a series of N-acylated derivatives including the following: 22d (2,3-dihydroxybenzoyl), 25 (2-hydroxybenzoyl), 27 (3,4-dihydroxybenzoyl), 29 (4'methyl-2,2'-bipyridine-4-carbonyl), 31 (epsilon-(L-alpha-aminoadipoyl)), 34 ((N'-2,3-dihydroxybenzoyl)-beta-alanyl), 35 (bromoacetyl), 36 ((6-purinylthio)acetyl), and 37 ((4-pyridylthio)acetyl). The results show that a-amino beta-lactones bearing an N-acyl group with an o- or p-hydroxybenzoyl moiety are especially prone to decomposition under aqueous conditions and that this effect is enhanced by replacement of the 4-nitrobenzyl group on the oxetanone ring of 1 with a methyl. The N-(3,4-dihydroxybenzoyl)L-threonine beta-lactone (27) converts slowly in the solid state to (4S,5S)-2-(3,4-dihydroxybenzoyl)-5-methyl-2-oxazoline-4-carboxylic acid (39b), which hydrolyzes rapidly in 4:1 CD3CN:D2O to O-(3,4-dihydroxybenzoyl)-L-allothreonine (38b). Direct hydrolysis of 27 to 38b under the same conditions has a half-life of 2.4 days. Preliminary assays for antibacterial activity indicate that 29 has nearly comparable activity to obafluorin(l) but is much more stable. The (2-nitrophenyl)sulfenyl p-lactones 14 and 41, as well as the N-(phenylsulfenyl)-L-threonine beta-lactone (44), are the most active agents in the biological assays.

  DOI：

  10.1021/jo00092a025
• 作为产物：
  描述：

  (对硝基苯基)丙酮酸 在 磷酸吡哆醛 、 3-[(4-氨基-2-甲基-5-嘧啶基)甲基]-4-甲基-5-[4,6,6-三羟基-4,6-二氧-3,5-二氧-4,6-二磷(五)己-1-基]噻唑-3-鎓 、 magnesium chloride 作用下， 以 aq. buffer 为溶剂， 反应 5.0h， 生成 (2S,3R)-2-Amino-3-hydroxy-4-(4-nitrophenyl)butanoic acid
  参考文献：
  名称：

  从非核糖体肽合成酶释放产物期间β-内酯的形成

  摘要：

  非核糖体肽合成酶（NRPS）是多域模块化生物合成装配线，可将氨基酸聚合成无数的具有生物活性的非核糖体肽（NRP）。NRPS硫酯酶（TE）域采用多种释放策略，通常通过水解，氨解或环化作用从末端模块上卸下硫酯束缚的聚合肽，以分别提供成熟的抗生素，分别为羧酸/酯，酰胺和内酰胺/内酯。在这里，我们报告了在TE介导的β-羟基硫酯的环化过程中，从NRPS组装生产线释放抗生素的obafluorin（Obi）的过程中，酶催化的高张力β-内酯环的形成。Obi NRPS（ObiF）包含一个I型TE结构域，该结构域具有一个罕见的催化半胱氨酸残基，该残基在β-内酯环的形成中起着直接作用。荧光假单胞菌ATCC 39502建立了β-内酯生物发生的一般策略。

  DOI：

  10.1038/nchembio.2374

文献信息

• Synthesis of (+)-obafluorin, a .beta.-lactone antibiotic
  作者：Christopher Lowe、Yunlong Pu、John C. Vederas

  DOI：10.1021/jo00027a006

  日期：1992.1

  Optically pure obafluorin (1), an antibacterial agent from Pseudomonas fluorescens, was synthesized via lactonization of N-[(2-nitrophenyl)sulfenyl]-(2S,3R)-2-amino-3-hydroxy-4-(4-nitrophenyl)butanoic acid (6), which was prepared in a stereospecific manner from 4-nitrophenylacetaldehyde and (S)-1-benzoyl-2-(tert-butyl)-3-methyl-4-imidazolidinone (4a).
• Immunity-Guided Identification of Threonyl-tRNA Synthetase as the Molecular Target of Obafluorin, a β-Lactone Antibiotic
  作者：Thomas A. Scott、Sibyl F. D. Batey、Patrick Wiencek、Govind Chandra、Silke Alt、Christopher S. Francklyn、Barrie Wilkinson

  DOI：10.1021/acschembio.9b00590

  日期：2019.12.20

  To meet the ever-growing demands of antibiotic discovery, new chemical matter and antibiotic targets are urgently needed. Many potent natural product antibiotics which were previously discarded can also provide lead molecules and drug targets. One such example is the structurally unique beta-lactone obafluorin, produced by Pseudomonas fluorescens ATCC 39502. Obafluorin is active against both Gram-positive and -negative pathogens; however, the biological target was unknown. We now report that obafluorin targets threonyl-tRNA synthetase, and we identify a homologue, ObaO, which confers immunity to the obafluorin producer. Disruption of obaO in P. fluorescens ATCC 39502 results in obafluorin sensitivity, whereas expression in sensitive E. coli strains confers resistance. Enzyme assays demonstrate that E. coli threonyl-tRNA synthetase is fully inhibited by obafluorin, whereas ObaO is only partly susceptible, exhibiting a very unusual partial inhibition mechanism. Altogether, our data highlight the utility of an immunity-guided approach for the identification of an antibiotic target de novo and will ultimately enable the generation of improved obafluorin variants.