| 220971-92-6

• 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
• CAS: 220971-92-6
• 化学式: C₇₄H₈₃Cl₂N₉O₂₈
• 分子量: 1617.42
• InChiKey: VEPIRAURXBZUHA-FQWPREGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.09
• 重原子数：
  113.0
• 可旋转键数：
  18.0
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  560.31
• 氢给体数：
  18.0
• 氢受体数：
  27.0

反应信息

• 作为反应物：
  描述：

  3-溴丙烯 、 在 碳酸氢钠 作用下， 以 二甲基亚砜 为溶剂， 生成 N,N'-dialloc vancomycin allyl ester
  参考文献：
  名称：

  疏水取代基在糖肽类抗生素生物活性中的作用

  摘要：

  DOI：

  10.1021/ja0027665
• 作为产物：
  描述：

  烯丙基琥珀酰亚胺基碳酸酯 、 盐酸万古霉素 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Model for Antibiotic Optimization via Neoglycosylation:  Synthesis of Liponeoglycopeptides Active against VRE

  摘要：

  The neoglycosylation of a methoxyamine-appended vancomycin aglycon with all possible N'-decanoylglucopyranose and N'-biphenoylglucopyranose regioisomers led to the production of a focused set of liponeoglycopeptide variants in good yields and with excellent stereoselectivity. High-throughput antibacterial assays employing a unique set of vancomycin-resistant Enterococci faecalis and Enterococci faecium clinical isolates revealed that the nature and regiochemistry of glycosyl lipidation modulated vancomycin-resistent Enterococci potency. In contrast to prior work with lipoglycopeptides, this study reveals the glucose C3' or C4' as the optimal position for neoglycopeptide lipidation. This purely chemical method for the diversification of the glycolipid portion of lipoglycopeptide antibiotics is simple to perform on a large scale, requires minimal synthetic effort in sugar donor preparation, and provides access to highly active antibiotics that are not easily prepared by other state-of-the-art methods.

  DOI：

  10.1021/ja068602r

文献信息

• Reconstruction of Vancomycin by Chemical Glycosylation of the Pseudoaglycon
  作者：Min Ge、Christopher Thompson、Daniel Kahne

  DOI：10.1021/ja982414m

  日期：1998.10.1
• Synthesis of Vancomycin from the Aglycon
  作者：Christopher Thompson、Min Ge、Daniel Kahne

  DOI：10.1021/ja983504u

  日期：1999.2.1

  Vancomycin-resistant bacterial strains pose a serious threat to human health. Efforts to overcome vancomycin resistance by modifying the natural product have shown that the carbohydrates help modulate biological activity. To explore the mechanisms by which the carbohydrates function, it would be useful to have access to vancomycin derivatives containing different disaccharides. We now describe the synthesis of vancomycin from a readily available protected aglycon. This chemistry lays the groundwork for wide-ranging investigations of the roles of the carbohydrates in the biological activity of vancomycin. Moreover, in developing methods to glycosylate vancomcyin, we have extended the utility of the sulfoxide glycosylation reaction considerably by making it possible to use unhindered esters as neighboring groups. The chemistry we describe may also have implications for how to improve some other glycosylation methods.
• Structure Diversification of Vancomycin through Peptide-Catalyzed, Site-Selective Lipidation: A Catalysis-Based Approach To Combat Glycopeptide-Resistant Pathogens
  作者：Sabesan Yoganathan、Scott J. Miller

  DOI：10.1021/jm501872s

  日期：2015.3.12

  The emergence of antibiotic-resistant infections highlights the need for novel antibiotic leads, perhaps with a broader spectrum of activity. Herein, we disclose a semisynthetic, catalytic approach for structure diversification of vancomycin. We have identified three unique peptide catalysts that exhibit site-selectivity for the lipidation of the aliphatic hydroxyls on vancomycin, generating three new derivatives 9a, 9b, and 9c. Incorporation of lipid chains into the vancomycin scaffold provides promising improvement of its bioactivity against vancomycin-resistant enterococci (Van A and Van B phenotypes of VRE). The MICs for 9a, 9b, and 9c against MRSA and VRE (Van B phenotype) range from 0.12 to 0.25 mu g/mL. We have also performed a structure-activity relationship (SAR) study to investigate the effect of lipid chain length at the newly accessible G(4)-OH derivatization site.