3-amino-N-pentylpropanamide | 271591-61-8

• 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: 3-amino-N-pentylpropanamide
• CAS: 271591-61-8
• 化学式: C₈H₁₈N₂O
• 分子量: 158.244
• InChiKey: BQWFAUQWNNKGDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  11
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-amino-N-pentylpropanamide 在 水 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 32.0h， 生成 (2R,3R)-2-hydroxy-3-(hydroxymethyl)-3-methyl-N-(3-oxo-3-(pentylamino)propyl)hex-5-enamide
  参考文献：
  名称：

  N-取代泛酰胺的孪生二烷基衍生物：合成和抗菌活性

  摘要：

  作为辅酶 A (CoA) 生物合成的关键前体，泛酸已被证明是构建该生物合成途径探针、研究 CoA 使用系统和设计具有抗菌活性的分子的有用骨架。对一种或多种抗生素具有抗性的细菌菌株的日益流行，促使人们重新关注具有新型抗菌作用模式的分子，例如 N 取代泛酰胺。尽管已经报道了许多衍生物，但大多数在末端 N-取代基处有所不同，而在 β-丙氨酸部分则较少。pantoyl 部分的修饰仅限于添加 ω-甲基。我们报告了 N 取代泛酰胺的合成路线，其中各种烷基取代基取代了孪生二甲基基团。我们的方法也适用于泛酸、泛酰巯基乙胺和 CoA 衍生物的合成。这里合成了一个新的 N 取代泛酰胺的小型文库。这些化合物中的大多数显示出对敏感和耐药的抗菌活性金黄色葡萄球菌。有趣的是，用烯丙基取代ProR甲基产生了一种新的 N 取代泛酰胺，这是迄今为止报道的最有效的。

  DOI：

  10.1016/j.bmc.2011.02.053
• 作为产物：
  描述：

  (9H-fluoren-9-yl)methyl 3-oxo-3-(pentylamino)propylcarbamate 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 3-amino-N-pentylpropanamide
  参考文献：
  名称：

  探索大肠杆菌泛酸激酶活性位点中底物结合所必需的结构基序

  摘要：

  辅酶 A (CoA) 生物合成酶已被用于生产各种 CoA 类似物，包括 CoA 依赖性酶的机械探针，例如参与脂肪酸生物合成的酶。这些酶对于激活泛酰胺类抗菌剂和最近报道的抗生素抗性抑制剂家族也很重要。在此我们报告了泛酸激酶选择性的研究，泛酸激酶是 CoA 生物合成的第一步和限速步骤。开发了一种强大的合成路线，以允许快速访问在 β-丙氨酸部分、羧酸盐或孪生二甲基基团上多样化的泛酸类似物的小型文库。所有衍生物均作为大肠杆菌泛酸激酶 ( Ec潘K）。四种衍生物，全是N-芳香族泛酰胺，被证明与作为Ec PanK底物的基准N-戊基泛酰胺 (N5-pan)等效，而另外两种也具有N-芳香族基团，是为此报道的一些最佳底物酶。这些数据为未来在生产有用的 CoA 类似物时设计 PanK 底物提供了见解。

  DOI：

  10.1016/j.bmc.2014.04.030

文献信息

• A cross-metathesis approach to novel pantothenamide derivatives
  作者：Jinming Guan、Matthew Hachey、Lekha Puri、Vanessa Howieson、Kevin J Saliba、Karine Auclair

  DOI：10.3762/bjoc.12.95

  日期：——

  Pantothenamides are known for their in vitro antimicrobial activity. Our group has previously reported a new stereoselective route to access derivatives modified at the geminal dimethyl moiety. This route however fails in the addition of large substituents. Here we report a new synthetic route that exploits the known allyl derivative, allowing for the installation of larger groups via cross-metathesis. The method was applied in the synthesis of a new pantothenamide with improved stability in human blood.

  泛酰胺因其体外抗微生物活性而闻名。我们的团队先前报道了一种新的立体选择性路径，可用于访问在伽玛二甲基基团上进行修饰的衍生物。然而，该路径在添加大的取代基时失败。在这里，我们报告了一种利用已知的烯丙基衍生物的新合成途径，通过交叉烯烃转化实现较大基团的安装。该方法已应用于合成一种新的泛酰胺，在人类血液中具有改善的稳定性。
• Variation in pantothenate kinase type determines the pantothenamide mode of action and impacts on coenzyme A salvage biosynthesis
  作者：Marianne de Villiers、Leanne Barnard、Lizbé Koekemoer、Jacky L. Snoep、Erick Strauss

  DOI：10.1111/febs.13013

  日期：2014.10

  N‐substituted pantothenamides are analogues of pantothenic acid, the vitamin precursor of CoA, and constitute a class of well‐studied bacterial growth inhibitors that show potential as new antibacterial agents. Previous studies have highlighted the importance of pantothenate kinase (PanK; EC 2.7.1.33) (the first enzyme of CoA biosynthesis) in mediating pantothenamide‐induced growth inhibition by one of two proposed mechanisms: first, by acting on the pantothenamides as alternate substrates (allowing their conversion into CoA antimetabolites, with subsequent effects on CoA‐ and acyl carrier protein‐dependent processes) or, second, by being directly inhibited by them (causing a reduction in CoA biosynthesis). In the present study we used structurally modified pantothenamides to probe whether PanKs interact with these compounds in the same manner. We show that the three distinct types of eubacterial PanKs that are known to exist (PanKI, PanKII and PanKIII) respond very differently and, consequently, are responsible for determining the pantothenamide mode of action in each case: although the promiscuous PanKI enzymes accept them as substrates, the highly selective PanKIIIs are resistant to their inhibitory effects. Most unexpectedly, Staphylococcus aureus PanK (the only known example of a bacterial PanKII) experiences uncompetitive inhibition in a manner that is described for the first time. In addition, we show that pantetheine, a CoA degradation product that closely resembles the pantothenamides, causes the same effect. This suggests that, in S. aureus, pantothenamides may act by usurping a previously unknown role of pantetheine in the regulation of CoA biosynthesis, and validates its PanK as a target for the development of new antistaphylococcal agents.
• Stereochemical modification of geminal dialkyl substituents on pantothenamides alters antimicrobial activity
  作者：Annabelle Hoegl、Hamed Darabi、Elisa Tran、Emelia Awuah、Eleanor S.C. Kerdo、Eric Habib、Kevin J. Saliba、Karine Auclair

  DOI：10.1016/j.bmcl.2014.06.013

  日期：2014.8

  Pantothenamides are N-substituted pantothenate derivatives which are known to exert antimicrobial activity through interference with coenzyme A (CoA) biosynthesis or downstream CoA-utilizing proteins. A previous report has shown that replacement of the ProR methyl group of the benchmark N-pentylpantothenamide with an allyl group (R-anti configuration) yielded one of the most potent antibacterial pantothenamides reported so far (MIC of 3.2 mu M for both sensitive and resistant Staphylococcus aureus). We describe herein a synthetic route for accessing the corresponding R-syn diastereomer using a key diastereoselective reduction with Baker's yeast, and report on the scope of this reaction for modified systems. Interestingly, whilst the R-anti diastereomer is the only one to show antibacterial activity, the R-syn isomer proved to be significantly more potent against the malaria parasite (IC50 of 2.4 +/- 0.2 mu M). Our research underlines the striking influence that stereochemistry has on the biological activity of pantothenamides, and may find utility in the study of various CoA-utilizing systems. (C) 2014 Published by Elsevier Ltd.
• Hyperbranched polymer conjugates via non-enzymatic cleavable linker
  申请人：Ascendis Pharma Growth Disorders Division A/S

  公开号：EP2090323B1

  公开（公告）日：2016-07-27
• US5594003A
  申请人：——

  公开号：US5594003A

  公开（公告）日：1997-01-14