1'-epi-showdomycin | 79934-05-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1'-epi-showdomycin
• 英文别名: Epishowdomycin；3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrrole-2,5-dione
• CAS: 79934-05-7
• 化学式: C₉H₁₁NO₆
• 分子量: 229.189
• InChiKey: FFLUMYXAPXARJP-XVFCMESISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,3,5-tri-O-benzyl-α-D-ribofuranosylethyne 在 palladium dichloride 氢氧化钾 、 氨 、 乙酸酐 、 三氯化硼 、 乙酰氯 、 mercury dichloride 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， -78.0~25.0 ℃ 、202.65 kPa 条件下， 反应 90.17h， 生成 1'-epi-showdomycin
  参考文献：
  名称：

  C-核苷研究。第13部分。涉及苄氧基参与的2,3,5-三-O-苄基-α（和β）-D-呋喃呋喃糖基乙炔的新合成以及α-Showdomycin的合成

  摘要：

  2,3,4,6-四- ö苄基d -glucitol（5）反应以甲苯p -磺酰基氯在吡啶中于60℃，以形成主要是呋喃产物2,3,6-三ö -苄基-1,4-脱水-D-葡萄糖醇（10）及其5-甲苯-对磺酸酯（11），但失去4- O-苄基。该吡喃产物四ö苄基1,5-脱水- d -glucitol preponderates当中间2,3,4,6-四ö -toluene- p -sulphonyl- d -glucitol（6）转化成其0–5氧阴离子。在新合成的2,3,5-tri- O中已经利用了苄氧基的参与苄基α（及β） - d -ribofuranosylethyne，（20）和（4），从2,3,4,5-四ö苄基醛基- d -核糖。描述了由（20）合成2-α- D-呋喃呋喃糖基马来酰亚胺（Showdomycin的α-异构体）。

  DOI：

  10.1039/p19810002267

文献信息

• Identification of a Pyrrole Intermediate Which Undergoes C‐Glycosidation and Autoxidation to Yield the Final Product in Showdomycin Biosynthesis
  作者：Daan Ren、Minje Kim、Shao‐An Wang、Hung‐wen Liu

  DOI：10.1002/anie.202105667

  日期：2021.7.26

  decarboxylation and deamination to afford showdomcyin after exposure to air. These results suggest that showdomycin could be an artifact due to aerobic isolation; however, the autoxidation may also serve to convert an otherwise inert product of the biosynthetic pathway to an electrophilic C-nucleotide thereby endowing showdomycin with its observed bioactivities.

  Showdomycin 是一种带有亲电马来酰亚胺碱基的C-核苷。本文介绍了秀多霉素的生物合成途径。该途径的初始阶段涉及非核糖体肽合成酶 (NRPS) 介导的 2-氨基-1 H-吡咯-5-羧酸中间体组装。该中间体易于空气氧化，因此它经历氧化脱羧产生马来酰亚胺的亚胺，其在酸化时又产生马来酰亚胺。还显示该吡咯中间体充当途径中C-糖苷酶 SdmA 的底物。与核糖 5-磷酸偶联后，生成的C-核苷在暴露于空气后经历了类似的氧化、脱羧和脱氨基作用以产生秀多霉素。这些结果表明，由于需氧分离，秀多霉素可能是一种人工产物。然而，自氧化也可用于将生物合成途径的惰性产物转化为亲电子C-核苷酸，从而赋予秀多霉素其观察到的生物活性。
• Subclass-Specific Labeling of Protein-Reactive Natural Products with Customized Nucleophilic Probes
  作者：Georg C. Rudolf、Maximilian F. Koch、Franziska A. M. Mandl、Stephan A. Sieber

  DOI：10.1002/chem.201405009

  日期：2015.2.23

  Herein small nucleophilic probes that attack electrophilic natural products and enhance their detection by HPLC‐UV and HPLC‐MS are introduced. A screen of diverse probe designs revealed one compound with a desired selectivity for epoxide‐ and maleimide‐based antibiotics. Correspondingly, the natural products showdomycin and phosphomycin could be selectively targeted in extracts of their natural producing

  天然产物代表了生物活性化合物的丰富来源，这些生物活性化合物构成了批准药物的很大一部分。其中包括带有亲电子支架的分子，例如迈克尔受体，β-内酰胺和环氧化物，它们基于其催化机理不可逆地抑制必需酶。在寻找新的生物活性分子时，当前方法受到已知化学实体的频繁重新发现的挑战。本文介绍了可攻击亲电子天然产物并通过HPLC-UV和HPLC-MS增强检测能力的小型亲核探针。通过对多种探针设计的筛选，发现了一种对环氧化物和马来酰亚胺基抗生素具有所需选择性的化合物。相应地，天然产物秀光霉素和磷霉素可在其天然生产生物的提取物中有选择性地靶向，相对于未修饰的对应物，经探针修饰的分子表现出更好的保留和MS检测。因此，该方法可能有助于发现小的亲电子分子，否则，它们很容易在复杂样品中被检测出来。
• Syntheses of Showdomycin andits Anomer Using<i>N</i>-(Triisopropylsilyl)pyrrole asa Synthetic Equivalent for the Maleimide C3-Anion
  作者：Martin G. Banwell、Natasha L. Hungerford、David J. Armitt

  DOI：10.1055/s-2003-41026

  日期：——

  Showdomycin (1) and its anomer (2) have been prepared in four steps fromreadily available trichloroacetimidate 9.The key step involves reaction of the last compound with the titlepyrrole 3 so as to form a chromatographically separable mixtureof the pyrrole C-glycosides 10 and 11. Thesepyrroles are desilylated then oxidized to the corresponding maleimidesusing PCC.

  昭和霉素（1）及其异构体（2）是由现成的三氯乙酰亚氨酸 9 分四个步骤制备而成的。关键步骤是将最后一种化合物与标题吡咯 3 反应，形成色谱上可分离的吡咯 C-糖苷混合物 10 和 11。这些吡咯经过脱硅处理，然后用 PCC 氧化成相应的马来酰亚胺。
• Two total syntheses of showdomycin and related studies
  作者：Anthony G. M. Barrett、Howard B. Broughton、Steven V. Attwood、A. A. Leslie Gunatilaka

  DOI：10.1021/jo00354a017

  日期：1986.2
• Showdomycin as a Versatile Chemical Tool for the Detection of Pathogenesis-Associated Enzymes in Bacteria
  作者：Thomas Böttcher、Stephan A. Sieber

  DOI：10.1021/ja909150y

  日期：2010.5.26

  Showdomycin is a potent nucleoside antibiotic that displays a high structural similarity to uridine and pseudouridine. No detailed target analysis of this very unusual electrophilic natural product has been carried out so far. To unravel its biological function, we synthesized a showdomycin probe that can be appended with a fluorophor or a biotin marker via click chemistry and identified diverse enzymes which were important for either the viability or virulence of pathogenic bacteria. Our results indicate that the antibiotic effect of showdomycin against Staphylococcus aureus may be due to the inhibition of various essential enzymes, especially MurA1 and MurA2, which are required for cell wall biosynthesis. Although real-time polymerase chain reaction revealed that the MurA2 gene was expressed equally in four S. aureus strains, our probe studies showed that MurA2 was activated in only one multiresistant S. aureus strain, and only this strain was resistant to elevated concentrations of the MurA inhibitor fosfomycin, suggesting its potential role as an antibiotic bypass mechanism in the case of MurA1 inhibition. Moreover, we utilized this tool to compare enzyme profiles of different pathogenic strains, which provided unique insights in regulatory differences as well as strain-specific signatures.