| 1378999-76-8

• 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
• CAS: 1378999-76-8
• 化学式: C₂₆H₃₃N₃O₇
• 分子量: 499.564
• InChiKey: MLQWZASQNROZEX-KNQAVFIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.06
• 重原子数：
  36.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  132.06
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  N,N’-双苄氧羰基-L-赖氨酸 、 D-丙氨酸甲酯盐酸盐 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 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成
  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

文献信息

• Catalytic Site-Selective Thiocarbonylations and Deoxygenations of Vancomycin Reveal Hydroxyl-Dependent Conformational Effects
  作者：Brandon S. Fowler、Kai M. Laemmerhold、Scott J. Miller

  DOI：10.1021/ja302692j

  日期：2012.6.13

  We have examined peptide-based catalysts for the site-selective thiocarbonylation of a protected form of vancomycin. Several catalysts were identified that either enhanced or altered the inherent selectivity profile exhibited by the substrate. Two catalysts, one identified through screening and another through rational design, were demonstrated to be effective on 0.50-g scale. Deoxygenations led ultimately to two new deoxy-vancomycin derivatives, and surprising conformational consequences of deoxygenation were revealed for one of the new compounds. These effects were mirrored in the biological activities of the new analogues and support a structural role for certain hydroxyls in the native structure.