黄荧菌素 | 92121-68-1

• 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
• 中文名称: 黄荧菌素
• 英文名称: obafluorin
• 英文别名: 2,3-dihydroxy-N-[(2R,3S)-2-[(4-nitrophenyl)methyl]-4-oxooxetan-3-yl]benzamide
• CAS: 92121-68-1
• 化学式: C₁₇H₁₄N₂O₇
• 分子量: 358.307
• InChiKey: AINNQKIVZOTQBB-KGLIPLIRSA-N

物化性质

• 溶解度：
  乙腈：>1mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  黄荧菌素 在 水 作用下， 以 乙腈 为溶剂， 反应 3600.0h， 生成 (2S,3S)-2-Amino-3-<<(2,3-dihydroxy)benzoyl>oxy>-4-(4-nitrophenyl)butanoic acid
  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：

  在 水 作用下， 生成 黄荧菌素
  参考文献：
  名称：

  Synthesis of (+)-obafluorin, a .beta.-lactone antibiotic

  摘要：

  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).

  DOI：

  10.1021/jo00027a006

文献信息

• LACTONE-BASED PROBES AND METHODS OF USE THEREOF
  申请人：REGENTS OF THE UNIVERSITY OF MINNESOTA

  公开号：US20180339972A1

  公开（公告）日：2018-11-29

  The invention provides a compound of formula I: or a salt thereof, wherein R 1 , R 2 , R 3 , R 4 , L 1 , L 2 and Y have any of the values described in the specification, as well as compositions comprising a compound of formula I. The compounds are useful for labeling penicillin-binding proteins (PBPs).

  该发明提供了一个式I的化合物： 或其盐，其中R 1 ，R 2 ，R 3 ，R 4 ，L 1 ，L 2 和Y具有规范中描述的任何值，以及包含式I的化合物的组合物。这些化合物可用于标记青霉素结合蛋白（PBPs）。
• β-Lactone formation during product release from a nonribosomal peptide synthetase
  作者：Jason E Schaffer、Margaret R Reck、Neha K Prasad、Timothy A Wencewicz

  DOI：10.1038/nchembio.2374

  日期：2017.7

  respectively. Here we report the enzyme-catalyzed formation of a highly strained β-lactone ring during TE-mediated cyclization of a β-hydroxythioester to release the antibiotic obafluorin (Obi) from an NRPS assembly line. The Obi NRPS (ObiF) contains a type I TE domain with a rare catalytic cysteine residue that plays a direct role in β-lactone ring formation. We present a detailed genetic and biochemical

  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。
• BETA-LACTONES AS ANTIBACTERIAL AGENTS
  申请人：Sieber Stephan A.

  公开号：US20110196027A1

  公开（公告）日：2011-08-11

  The present invention relates to specific beta-lactone compounds and compositions thereof for the treatment of infections, such as, e.g., infections with bacteria or infections with protozoa, in particular infections with Gram-positive and/or Gram-negative bacteria and of infectious diseases caused by or related to Gram-positive and/or Gram-negative bacteria, and to the modulation of virulence of Gram-positive and/or Gram-negative bacteria or of protozoa by specific beta-lactone compounds. The invention further relates to the use of the compounds or compositions for preventing or eliminating biofilms.

  本发明涉及特定的β-内酰胺类化合物及其组合物，用于治疗感染，例如细菌感染或原虫感染，特别是革兰氏阳性和/或革兰氏阴性细菌感染以及由革兰氏阳性和/或革兰氏阴性细菌引起或相关的传染病，并且涉及通过特定的β-内酰胺类化合物调节革兰氏阳性和/或革兰氏阴性细菌或原虫的毒力。本发明还涉及使用这些化合物或组合物预防或消除生物膜。
• Processes and host cells for genome, pathway, and biomolecular engineering
  申请人：enEvolv, Inc.

  公开号：US10370654B2

  公开（公告）日：2019-08-06

  The present disclosure provides compositions and methods for genomic engineering.

  本公开提供了基因组工程的组合物和方法。
• Chemoenzymatic synthesis of peptide beta-lactones and beta-hydroxy acids
  申请人：Wencewicz Timothy A.

  公开号：US10655153B2

  公开（公告）日：2020-05-19

  Methods of producing peptide beta-lactones and beta-hydroxy acids are disclosed that include contacting a beta-hydroxy-alpha-amino acid, an aryl carrier protein (ObiD), and ATP with a non-ribosomal protein synthetase. A continuous flow reactor is disclosed that includes an elongate conduit with at least one region that includes a first region with a non-ribosomal protein synthetase immobilized to a substrate. The non-ribosomal protein synthetase of the continuous flow reactor is configured to contact a flow of a reaction mixture that includes a beta-hydroxy-alpha-amino acid and an aryl carrier protein. The non-ribosomal protein synthetase is further configured to release a peptide beta-lactone into the flow of the reaction mixture.

  本发明公开了生产β-内酯肽和β-羟基酸的方法，包括将β-羟基-α-氨基酸、芳基载体蛋白（ObiD）和ATP与非核糖体蛋白合成酶接触。本发明公开了一种连续流反应器，它包括一个细长的导管，导管上至少有一个区域，该区域包括固定在底物上的非核糖体蛋白合成酶的第一区域。连续流动反应器的非核糖体蛋白合成酶被配置为接触反应混合物流，该混合物包括β-羟基-α-氨基酸和芳基载体蛋白。非核糖体蛋白合成酶的进一步配置是将肽β-内酯释放到反应混合物流中。