(8S,11S,14S)-14-[[2-[[(2R)-2-[[(2R)-2-[hexadecanoyl(methyl)amino]-3-hydroxypropanoyl]amino]propanoyl]amino]acetyl]-methylamino]-3-hydroxy-11-methyl-10,13-dioxo-18-phosphonooxy-9,12-diazatricyclo[13.3.1.12,6]icosa-1(18),2,4,6(20),15(19),16-hexaene-8-carboxylic acid | 1458631-78-1

• 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: (8S,11S,14S)-14-[[2-[[(2R)-2-[[(2R)-2-[hexadecanoyl(methyl)amino]-3-hydroxypropanoyl]amino]propanoyl]amino]acetyl]-methylamino]-3-hydroxy-11-methyl-10,13-dioxo-18-phosphonooxy-9,12-diazatricyclo[13.3.1.12,6]icosa-1(18),2,4,6(20),15(19),16-hexaene-8-carboxylic acid
• CAS: 1458631-78-1
• 化学式: C₄₆H₆₉N₆O₁₄P
• 分子量: 961.059
• InChiKey: SBLUJGBWFBZTKA-JBWZRHCTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  67
• 可旋转键数：
  25
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  302
• 氢给体数：
  9
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  benzyl (4S,7S,10S)-26-(benzyloxy)-10-(2-((R)-2-((R)-3-(benzyloxy)-2-(N-methylpalmitamido)propanamido)propanamido)-N-methylacetamido)-16-((bis(benzyloxy)phosphoryl)oxy)-7-methyl-6,9-dioxo-5,8-diaza-1,2(1,3)-dibenzenacyclodecaphane-4-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 甲酸 为溶剂， 反应 12.0h， 以5 mg的产率得到(8S,11S,14S)-14-[[2-[[(2R)-2-[[(2R)-2-[hexadecanoyl(methyl)amino]-3-hydroxypropanoyl]amino]propanoyl]amino]acetyl]-methylamino]-3-hydroxy-11-methyl-10,13-dioxo-18-phosphonooxy-9,12-diazatricyclo[13.3.1.12,6]icosa-1(18),2,4,6(20),15(19),16-hexaene-8-carboxylic acid
  参考文献：
  名称：

  Efforts toward broadening the spectrum of arylomycin antibiotic activity

  摘要：

  New antibiotics are needed, and one source may be 'latent' antibiotics, natural products whose once broad-spectrum activity is currently limited by the evolution of resistance in nature. We have identified a potential class of latent antibiotics, the arylomycins, which are lipopeptides with a C-terminal macrocycle that target signal peptidase and whose spectrum is limited by a resistance-conferring mutation in many bacteria. Herein, we report the synthesis and evaluation of several arylomycin derivatives, and demonstrate that both C-terminal homologation with a glycyl aldehyde and addition of a positive charge to the macrocycle increase the activity and spectrum of the arylomycin scaffold. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.026

文献信息

• Efforts toward broadening the spectrum of arylomycin antibiotic activity
  作者：Jian Liu、Peter A. Smith、Danielle Barrios Steed、Floyd Romesberg

  DOI：10.1016/j.bmcl.2013.08.026

  日期：2013.10

  New antibiotics are needed, and one source may be 'latent' antibiotics, natural products whose once broad-spectrum activity is currently limited by the evolution of resistance in nature. We have identified a potential class of latent antibiotics, the arylomycins, which are lipopeptides with a C-terminal macrocycle that target signal peptidase and whose spectrum is limited by a resistance-conferring mutation in many bacteria. Herein, we report the synthesis and evaluation of several arylomycin derivatives, and demonstrate that both C-terminal homologation with a glycyl aldehyde and addition of a positive charge to the macrocycle increase the activity and spectrum of the arylomycin scaffold. (C) 2013 Elsevier Ltd. All rights reserved.