N-(2-hydroxy-ethyl) pantothenamide | 17968-81-9

• 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: N-(2-hydroxy-ethyl) pantothenamide
• 英文别名: oxypantetheine；D-pantothenic acid-(2-hydroxy-ethylamide)；N-D-Pantoyl-β-alanin-(2-hydroxy-aethylamid)；D-Pantothensaeure-(2-hydroxy-aethylamid)；D-Oxypantethein；Pantothenamide monoethanolamide；(2R)-2,4-dihydroxy-N-[3-(2-hydroxyethylamino)-3-oxopropyl]-3,3-dimethylbutanamide
• CAS: 17968-81-9
• 化学式: C₁₁H₂₂N₂O₅
• 分子量: 262.306
• InChiKey: GHNDUMIFUDKMSF-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  119
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(2-hydroxy-ethyl) pantothenamide 在 pyruvate kinase 、 PanK 、 5’-三磷酸腺苷 作用下， 生成 D-Oxy-pantethein-4'-phosphat
  参考文献：
  名称：

  X射线结构确定底物结合的氧酯类似物配合物揭示的热狗折叠硫酯酶PA1618的催化机理

  摘要：

  晶体结构和酶机制：热狗折叠硫酯酶在细胞过程中起着不可或缺的作用。然而，仍然需要更好的抑制剂来帮助阐明这些酶。在这里，我们提供了一条通往苯甲酰-OdCoA和铜绿假单胞菌硫酯酶PA1618与苯甲酰-OdCoA和苯甲酰-CoA结合的晶体结构的合成途径。

  DOI：

  10.1002/cbic.201700322
• 作为产物：
  描述：

  3-((4R)-2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxane-4-carboxamido)propanoic acid 在 10 wt% Pd(OH)2 on carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-(2-hydroxy-ethyl) pantothenamide
  参考文献：
  名称：

  Trapping of Intermediates with Substrate Analog HBOCoA in the Polymerizations Catalyzed by Class III Polyhydroxybutyrate (PHB) Synthase from Allochromatium Vinosum

  摘要：

  Polyhydroxybutyrate (PHB) synthases (PhaCs) catalyze the formation of biodegradable PHB polymers that are considered as an ideal alternative to petroleum-based plastics. To provide strong evidence for the preferred mechanistic model involving covalent and noncovalent intermediates, a substrate analog HBOCoA was synthesized chemoenzymatically. Substitution of sulfur in the native substrate HBCoA with an oxygen in HBOCoA enabled detection of (HB)nOCoA (n = 2-6) intermediates when the polymerization was catalyzed by wild-type (wt-)PhaEC(Av) at 5.84 h(-1). This extremely slow rate is due to thermodynamically unfavorable steps that involve the formation of enzyme-bound PHB species (thioesters) from corresponding CoA oxoesters. Synthesized standards (HB)(n)OCoA (n = 2-3) were found to undergo both reacylation and hydrolysis catalyzed by the synthase. Distribution of the hydrolysis products highlights the importance of the penultimate ester group as previously suggested. Importantly, the reaction between primed synthase [H-3]-sT-PhaEC(Av) and HBOCoA yielded [H-3]-sTet-O-CoA at a rate constant faster than 17.4 s(-1), which represents the first example that a substrate analog undergoes PHB chain elongation at a rate close to that of the native substrate (65.0 s(-1)). Therefore, for the first time with a wt-synthase, strong evidence was obtained to support our favored PHB chain elongation model.

  DOI：

  10.1021/cb5009958

文献信息

• Development of a method for the parallel synthesis and purification of N-substituted pantothenamides, known inhibitors of coenzyme A biosynthesis and utilization
  作者：Marianne van Wyk、Erick Strauss

  DOI：10.1039/b811086g

  日期：——

  analogues which have been shown to act as inhibitors of coenzyme A biosynthesis and utilization, especially by blocking fatty acid metabolism through formation of inactive acyl carrier proteins. To fully explore the chemical diversity and inhibitory potential of these analogues we have developed a simple method for the parallel synthesis and purification of any number of pantothenamides from a single precursor

  N-取代的泛酰胺是一类泛酸类似物，已被证明可作为辅酶A生物合成和利用的抑制剂，特别是通过形成无活性的酰基载体蛋白来阻止脂肪酸代谢。为了全面探索这些类似物的化学多样性和抑制潜力，我们开发了一种简单的方法，用于从单个前体中并行合成和纯化任意数量的泛酰胺，随后评估了这些化合物的小文库作为细菌生长的抑制剂，以证明该方法的潜力和实用性。
• Investigations on Pantothenic Acid and Its Related Compounds. XIII. Chemical Studies. (6). Syntheses of Homopantethine and Some Other Pantethine Analogs
  作者：OSAMU NAGASE、HIROAKI TAGAWA、MASAO SHIMIZU

  DOI：10.1248/cpb.16.977

  日期：——

  Four pantethine analogs (homopantethine (VII), α-methyl-(XIIIb) and β-methyl-pantethine (XIIIc), and oxypantetheine (XVI)) were prepared. Synthesis of VII from D-pantothenonitrile (I) and homocysteamine by using the thiazine derivative (III) as an intermediate was established. XIIIb and XIIIc were synthesized by the thiazoline method described previously, and XVI by the general method.

  制备了四种泛硫乙胺类似物（高泛硫乙胺（VII），α-甲基泛硫乙胺（XIIIb）和β-甲基泛硫乙胺（XIIIc），以及氧化泛硫乙胺（XVI））。通过使用噻嗪衍生物（III）作为中间体，从D-泛硫腈（I）和高胱胺合成VII。使用先前描述的噻唑啉方法合成XIIIb和XIIIc，通过常规方法合成XVI。
• Activity of Fatty Acid Biosynthesis Initiating Ketosynthase FabH with Acetyl/Malonyl-oxa/aza(dethia)CoAs
  作者：Trevor J. Boram、Aaron B. Benjamin、Amanda Silva de Sousa、Lee M. Stunkard、Taylor A. Stewart、Timothy J. Adams、Nicholas A. Craft、Kevin G. Velázquez-Marrero、Jianheng Ling、Jaelen N. Nice、Jeremy R. Lohman

  DOI：10.1021/acschembio.2c00667

  日期：2023.1.20

  with mutant FabH C112Q that mimics the acyl-enzyme intermediate allowing dissection of the decarboxylation reaction. The acetyl- and malonyl-oxa(dethia)CoA analogues undergo extremely slow hydrolysis in the presence of FabH or the C112Q mutant. Decarboxylation of malonyl-oxa(dethia)CoA by FabH or C112Q mutant was not detected. The amide analogues were completely stable to enzyme activity. In enzyme assays

  脂肪酸和聚酮生物合成酶利用酰基硫酯和丙二酰硫酯的反应性进行催化。一个典型的例子是 FabH，它在许多细菌和植物中启动脂肪酸生物合成。 FabH 与乙酰辅酶 A 进行酰基转移酶反应，生成乙酰基-S -FabH 酰基酶中间体，随后与酰基载体蛋白 (ACP) 携带的丙二酰硫酯进行脱羧克莱森缩合。我们设想 FabH 与底物类似物的晶体结构可以深入了解支撑不同反应的构象变化和酶/底物相互作用。在这里，我们用酯或酰胺代替硫酯合成了乙酰/丙二酰辅酶A类似物，并表征了它们作为大肠杆菌FabH 底物或抑制剂的稳定性和行为，为结构研究提供信息。我们还用突变体 FabH C112Q 表征了类似物，它模拟酰基酶中间体，允许解析脱羧反应。在 FabH 或 C112Q 突变体存在的情况下，乙酰基和丙二酰基氧杂（脱硫）CoA 类似物会发生极其缓慢的水解。未检测到 FabH 或 C112Q 突变体对丙二酰氧 (dethia)CoA
• Pantethine inhibitors
  申请人：PARKE DAVIS &

  公开号：US02807644A1

  公开（公告）日：1957-09-24
• Catalytic Mechanism of the Hotdog-Fold Thioesterase PA1618 Revealed by X-ray Structure Determination of a Substrate-Bound Oxygen Ester Analogue Complex
  作者：John A. Latham、Tianyang Ji、Kaila Matthews、Patrick S. Mariano、Karen N. Allen、Debra Dunaway-Mariano

  DOI：10.1002/cbic.201700322

  日期：2017.10.5

  Crystal structures and enzyme mechanisms: Hotdog‐fold thioesterases play integral roles in cellular processes; however, there remains a need for better inhibitors to aid in the mechanistic elucidation of these enzymes. Here we provide a synthetic route to benzoyl‐OdCoA and crystal structures of the Pseudomonas aeruginosa thioesterase PA1618 bound to benzoyl‐OdCoA and phenacyl‐CoA.

  晶体结构和酶机制：热狗折叠硫酯酶在细胞过程中起着不可或缺的作用。然而，仍然需要更好的抑制剂来帮助阐明这些酶。在这里，我们提供了一条通往苯甲酰-OdCoA和铜绿假单胞菌硫酯酶PA1618与苯甲酰-OdCoA和苯甲酰-CoA结合的晶体结构的合成途径。