Cbz-Lys(Cbz)-D-Ala-D-Pmh-ONBu₄ | 1378999-80-4

• 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: Cbz-Lys(Cbz)-D-Ala-D-Pmh-ONBu₄
• 英文别名: Cbz-Lys(Cbz)-^DAla-^Dp-(methyl)histidine-ONBu₄
• CAS: 1378999-80-4
• 化学式: C₁₆H₃₆N*C₃₂H₃₉N₆O₈
• 分子量: 878.166
• InChiKey: GNDXNNUOGPOFBO-RKSSLGDMSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  63.0
• 可旋转键数：
  29.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  192.81
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 22.0h， 生成 Cbz-Lys(Cbz)-D-Ala-D-Pmh-ONBu₄
  参考文献：
  名称：

  Structure Diversification of Vancomycin through Peptide-Catalyzed, Site-Selective Lipidation: A Catalysis-Based Approach To Combat Glycopeptide-Resistant Pathogens

  摘要：

  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.

  DOI：

  10.1021/jm501872s
• 作为试剂：
  描述：

  、 氯磷酸二苯酯 在 Cbz-Lys(Cbz)-D-Ala-D-Pmh-ONBu₄ 、 1,2,2,6,6-五甲基哌啶 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.14h， 以42%的产率得到
  参考文献：
  名称：

  Asymmetric Catalysis at a Distance: Catalytic, Site-Selective Phosphorylation of Teicoplanin

  摘要：

  We report three distinct, peptide-based catalysts that enable site-selective phosphorylation of three distinct hydroxyl groups within the complex glycopeptide antibiotic teicoplanin A(2)-2. Two of the catalysts are based on a design that capitalizes on a catalyst substrate interaction that mimics the biological mechanism of action for teicoplanin. These catalysts are based on a DXaa-DXaa peptide motif that is known to target the teicoplanin structure in a specific manner. The third was identified through evaluation of a set of catalysts that had been developed for historically distinct projects. Each catalyst contains additional functionality designed to dispose a catalytic moiety (a nudeophilic alkylimidazole) at a different region of the glycopeptide structure. A combination of mass spectrometry and 2D-NMR spectroscopy allowed structural assignment of the distinct phosphorylated teicoplanin derivatives. Mechanistic studies are also reported that support the hypotheses that led to the discovery of the catalysts. In this manner, small molecule catalysts have been achieved that allow rational, catalytic control over reactions at sites that are separated by 11.6, 16.5, and nearly 17.7 angstrom, based on the X-ray crystal structure of teicoplanin A(2)-2. Finally, we report the biological activity of the new phosphorylated teicoplanin analogs and compare the results to the natural product itself.

  DOI：

  10.1021/ja406067v