1,3,2',6'-tetrakis(n-benzyloxycarbonyl)-5,6-O-cyclohexyl-3',4'-di-O-methoxymethylneamine | 419573-38-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 1,3,2',6'-tetrakis(n-benzyloxycarbonyl)-5,6-O-cyclohexyl-3',4'-di-O-methoxymethylneamine
• CAS: 419573-38-9
• 化学式: C₅₄H₆₆N₄O₁₆
• 分子量: 1027.14
• InChiKey: VXNPWFMTSABQAM-YRQHCFSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.73
• 重原子数：
  74.0
• 可旋转键数：
  21.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  227.16
• 氢给体数：
  4.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  1,3,2',6'-tetrakis(n-benzyloxycarbonyl)-5,6-O-cyclohexyl-3',4'-di-O-methoxymethylneamine 在 咪唑 、 4-二甲氨基吡啶 、 lithium hydroxide 、 四丁基氟化铵 、 四丁基碘化铵 、 sodium hydride 、 臭氧 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 57.67h， 生成 3,2',6'-tris(N-benzyloxycarbonyl)-1-N-tert-butoxylcarbonyl-5,3',4'-tri-O-methoxymethyl-6-O-(2-oxoethyl)neamine
  参考文献：
  名称：

  Design of Novel Antibiotics that Bind to the Ribosomal Acyltransfer Site

  摘要：

  The structure of neamine bound to the A site of the bacterial ribosomal RNA was used in the design of novel aminoglycosides. The design took into account stereo and electronic contributions to interactions between RNA and aminoglycosides, as well as a random search of 273 000 compounds from the Cambridge structural database and the National Cancer Institute 3-D database that would fit in the ribosomal aminoglycoside-binding pocket. A total of seven compounds were designed and subsequently synthesized, with the expectation that they would bind to the A-site RNA. Indeed, all synthetic compounds were found to bind to the target RNA comparably to the parent antibiotic neamine, with dissociation constants in the lower micromolar range. The synthetic compounds were evaluated for antibacterial activity against a set of important pathogenic bacteria. These designer antibiotics showed considerably enhanced antibacterial activities against these pathogens, including organisms that hyperexpressed resistance enzymes to aminoglycosides. Furthermore, analyses of four of the synthetic compounds with two important purified resistance enzymes for aminoglycosides indicated that the compounds were very poor substrates; hence the activity of these synthetic antibiotics does not appear to be compromised by the existing resistance mechanisms, as supported by both in vivo and in vitro experiments. The design principles disclosed herein hold the promise of the generation of a large series of designer antibiotics uncompromised by the existing mechanisms of resistance.

  DOI：

  10.1021/ja011695m
• 作为产物：
  描述：

  在 甲醇 、 四丁基碘化铵 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 1,3,2',6'-tetrakis(n-benzyloxycarbonyl)-5,6-O-cyclohexyl-3',4'-di-O-methoxymethylneamine
  参考文献：
  名称：

  Design of Novel Antibiotics that Bind to the Ribosomal Acyltransfer Site

  摘要：

  The structure of neamine bound to the A site of the bacterial ribosomal RNA was used in the design of novel aminoglycosides. The design took into account stereo and electronic contributions to interactions between RNA and aminoglycosides, as well as a random search of 273 000 compounds from the Cambridge structural database and the National Cancer Institute 3-D database that would fit in the ribosomal aminoglycoside-binding pocket. A total of seven compounds were designed and subsequently synthesized, with the expectation that they would bind to the A-site RNA. Indeed, all synthetic compounds were found to bind to the target RNA comparably to the parent antibiotic neamine, with dissociation constants in the lower micromolar range. The synthetic compounds were evaluated for antibacterial activity against a set of important pathogenic bacteria. These designer antibiotics showed considerably enhanced antibacterial activities against these pathogens, including organisms that hyperexpressed resistance enzymes to aminoglycosides. Furthermore, analyses of four of the synthetic compounds with two important purified resistance enzymes for aminoglycosides indicated that the compounds were very poor substrates; hence the activity of these synthetic antibiotics does not appear to be compromised by the existing resistance mechanisms, as supported by both in vivo and in vitro experiments. The design principles disclosed herein hold the promise of the generation of a large series of designer antibiotics uncompromised by the existing mechanisms of resistance.

  DOI：

  10.1021/ja011695m