9-fluorenylmethyl ester of glutaryl-β-alanine | 552891-69-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 9-fluorenylmethyl ester of glutaryl-β-alanine
• 英文别名: HO-Glut-β-Ala-OFm
• CAS: 552891-69-7
• 化学式: C₂₂H₂₃NO₅
• 分子量: 381.428
• InChiKey: UEDVJGPCDNZCBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  28.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  92.7
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  9-fluorenylmethyl ester of glutaryl-β-alanine 在 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.75h， 生成 3-{4-[2-(9H-Fluoren-9-ylmethoxycarbonyl)-ethylcarbamoyl]-butyrylamino}-propionic acid
  参考文献：
  名称：

  Multivalent Drug Design. Synthesis and In Vitro Analysis of an Array of Vancomycin Dimers

  摘要：

  The design, synthesis, and in vitro microbiological analysis of an array of forty covalently linked vancomycin dinners are reported. This work was undertaken to systematically probe the impact of linkage orientation and linker length on biological activity against susceptible and drug-resistant Gram-positive pathogens. To prepare the array, monomeric vancomycin synthons were linked through four distinct positions of the glycopeptide (C-terminus (C), N-terminus (N), vancosamine residue (V), and resorcinol ring (R)) in 10 unique pairwise combinations. Amphiphilic, peptide-based linkers of four different lengths (111, 19, 27, and 43 total atoms) were employed. Both linkage orientation and linker length were found to affect in vitro antibacterial potency. The V-V series displayed the greatest potency against vancomycin-susceptible organisms and vancomycin-resistant Enterococcus faecalis (VRE) of VanB phenotype, while the C-C, C-V, and V-R series displayed the most promising broad-spectrum activity that included VRE of VanA phenotype. Dimers bearing the shortest linkers were in all cases preferred for activity against VRE. The effects of linkage orientation and linker length on in vitro potency were not uniform; for example, (1) no single compound displayed activity that was superior against all test organisms to that of vancomycin or the other dimers, (2) linker length effects varied with test organism, and (3) whereas one-half of the dimers were more potent than vancomycin against methicillin-susceptible Staphylococcus aureus (MSSA), only one dimer was more potent against methicillin-resistant S. aureus (MRSA) and glycopeptide-intermediate susceptible S. aureus (GISA). In interpreting the results, we have considered the potential roles of multivalency and of other phenomena.

  DOI：

  10.1021/ja021273s
• 作为产物：
  描述：

  9-芴甲醇 在 4-二甲氨基吡啶 、 碳酸二异丙酯 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 43.0h， 生成 9-fluorenylmethyl ester of glutaryl-β-alanine
  参考文献：
  名称：

  Multivalent Drug Design. Synthesis and In Vitro Analysis of an Array of Vancomycin Dimers

  摘要：

  The design, synthesis, and in vitro microbiological analysis of an array of forty covalently linked vancomycin dinners are reported. This work was undertaken to systematically probe the impact of linkage orientation and linker length on biological activity against susceptible and drug-resistant Gram-positive pathogens. To prepare the array, monomeric vancomycin synthons were linked through four distinct positions of the glycopeptide (C-terminus (C), N-terminus (N), vancosamine residue (V), and resorcinol ring (R)) in 10 unique pairwise combinations. Amphiphilic, peptide-based linkers of four different lengths (111, 19, 27, and 43 total atoms) were employed. Both linkage orientation and linker length were found to affect in vitro antibacterial potency. The V-V series displayed the greatest potency against vancomycin-susceptible organisms and vancomycin-resistant Enterococcus faecalis (VRE) of VanB phenotype, while the C-C, C-V, and V-R series displayed the most promising broad-spectrum activity that included VRE of VanA phenotype. Dimers bearing the shortest linkers were in all cases preferred for activity against VRE. The effects of linkage orientation and linker length on in vitro potency were not uniform; for example, (1) no single compound displayed activity that was superior against all test organisms to that of vancomycin or the other dimers, (2) linker length effects varied with test organism, and (3) whereas one-half of the dimers were more potent than vancomycin against methicillin-susceptible Staphylococcus aureus (MSSA), only one dimer was more potent against methicillin-resistant S. aureus (MRSA) and glycopeptide-intermediate susceptible S. aureus (GISA). In interpreting the results, we have considered the potential roles of multivalency and of other phenomena.

  DOI：

  10.1021/ja021273s