(S)-4-(4-(2-((tert-butoxycarbonyl)amino)-3-methoxy-3-oxopropyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1446512-90-8

• 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: (S)-4-(4-(2-((tert-butoxycarbonyl)amino)-3-methoxy-3-oxopropyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
• 英文别名: 4-(4-((N-tert-butoxycarbonyl)-L-alanine methyl ester-3-yl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole-2-oxide；methyl (2S)-3-[4-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 1446512-90-8
• 化学式: C₂₃H₂₅N₃O₉S
• 分子量: 519.532
• InChiKey: OHOGWYRCJYVMAL-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  168
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-4-(4-(2-((tert-butoxycarbonyl)amino)-3-methoxy-3-oxopropyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以90%的产率得到(S)-4-(4-(2-((tert-butoxycarbonyl)amino)-2-carboxyethyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
  参考文献：
  名称：

  Novel amino acids: synthesis of furoxan and sydnonimine containing amino acids and peptides as potential nitric oxide releasing motifs

  摘要：

  将呋喃噁唑和吡啶亚胺环系统引入氨基酸侧链的工作通过制备四种具有这些释放一氧化氮结构的新型氨基酸得到了证明。N-((4-硝基苯氧)羧基)-3-苯基吡啶亚胺9和双（苯基磺酰）呋喃噁唑10是将杂环侧链引入适当的胺和醇功能的关键中间体。呋喃噁唑5和7均显示出基于亚硝酸盐生成的NO释放。采用正交氨基酸保护基团策略，证明这些氨基酸可以被嵌入肽框架中。作为示例，这些氨基酸被置于几个三肽结构的中心。Griess试验显示，这些氨基酸在存在γ-谷胱甘肽（GST）时释放NO。

  DOI：

  10.1039/c3ob41047a
• 作为产物：
  描述：

  Boc-L-酪氨酸甲酯 、 呋咱氮氧化物供体 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以86%的产率得到(S)-4-(4-(2-((tert-butoxycarbonyl)amino)-3-methoxy-3-oxopropyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
  参考文献：
  名称：

  Novel amino acids: synthesis of furoxan and sydnonimine containing amino acids and peptides as potential nitric oxide releasing motifs

  摘要：

  将呋喃噁唑和吡啶亚胺环系统引入氨基酸侧链的工作通过制备四种具有这些释放一氧化氮结构的新型氨基酸得到了证明。N-((4-硝基苯氧)羧基)-3-苯基吡啶亚胺9和双（苯基磺酰）呋喃噁唑10是将杂环侧链引入适当的胺和醇功能的关键中间体。呋喃噁唑5和7均显示出基于亚硝酸盐生成的NO释放。采用正交氨基酸保护基团策略，证明这些氨基酸可以被嵌入肽框架中。作为示例，这些氨基酸被置于几个三肽结构的中心。Griess试验显示，这些氨基酸在存在γ-谷胱甘肽（GST）时释放NO。

  DOI：

  10.1039/c3ob41047a

文献信息

• Identification of New Nitric Oxide-Donating Peptides with Dual Biofilm Eradication and Antibacterial Activities for Intervention of Device-Related Infections
  作者：Yue Fei、Jianbing Wu、Hong-Wei An、Kai Zhu、Bo Peng、Junquan Cai、Yihua Zhang、Li-Li Li、Hao Wang、Zhangjian Huang

  DOI：10.1021/acs.jmedchem.9b01832

  日期：2020.9.10

  Implantable medical device-related infections with biofilms have become a significant challenge in clinics. Based on the potential bacteria biofilm dispersing effect of nitric oxide (NO) and the unique antibacterial activity of antimicrobial peptides (AMP), we synthesized five peptides and selected the most potent one to conjugate its N-terminal with a furoxan moiety to offer a hitherto unknown NO-donating antimicrobial peptide (FOTyr-AMP), which exhibited Staphylococcus aureus and Escherichia coli biofilm dispersion and eradication, and potent antibacterial activities in vitro. In an implanted biofilm infection mice model, topical subcutaneous injection of FOTyr-AMP allowed synergetic eradication of bacterial biofilms and potent antibacterial activity, superior to the antibiotic cephalosporin C. Given the low hemolysis effect, little influence on the blood pressure, and potent in vivo efficacy of FOTyr-AMP, it is clear that subcutaneous administration of FOTyr-AMP could be a promising approach for the intervention of medical device-related biofilm infections with desirable safety.
• Novel amino acids: synthesis of furoxan and sydnonimine containing amino acids and peptides as potential nitric oxide releasing motifs
  作者：Andrew Nortcliffe、Nigel P. Botting、David O'Hagan

  DOI：10.1039/c3ob41047a

  日期：——

  The incorporation of furoxan and sydnonimine ring systems into amino acid side chains is demonstrated with the preparation of four novel amino acids which carry these nitric oxide-releasing motifs. N-((4-Nitrophenoxy)carbonyl)-3-phenylsydnonimine 9 and bis(phenylsulfonyl)furoxan 10 are the key intermediates for introducing the heterocycle side chains onto appropriate amine and alcohol functionalities respectively. Furoxan 5 and 7 both displayed NO release based on determination of nitrite production. Orthogonal amino acid protecting group strategies were deployed to demonstrate that the amino acids could be incorporated into peptide frameworks. By way of demonstration the amino acids were placed centrally into several tripeptide motifs. Griess test assays showed that these amino acids released NO in the presence of γ-glutathione (GST).

  将呋喃噁唑和吡啶亚胺环系统引入氨基酸侧链的工作通过制备四种具有这些释放一氧化氮结构的新型氨基酸得到了证明。N-((4-硝基苯氧)羧基)-3-苯基吡啶亚胺9和双（苯基磺酰）呋喃噁唑10是将杂环侧链引入适当的胺和醇功能的关键中间体。呋喃噁唑5和7均显示出基于亚硝酸盐生成的NO释放。采用正交氨基酸保护基团策略，证明这些氨基酸可以被嵌入肽框架中。作为示例，这些氨基酸被置于几个三肽结构的中心。Griess试验显示，这些氨基酸在存在γ-谷胱甘肽（GST）时释放NO。