1,3,2',6'-tetrakis(N-benzyloxycarbonyl)-5,6-O-cyclohexylideneneamine | 55728-75-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,3,2',6'-tetrakis(N-benzyloxycarbonyl)-5,6-O-cyclohexylideneneamine
• 英文别名: 1,3,2',6'-tetra(benzyloxycarbonyl)-5,6-O-(cyclohexylidene)neamine；tetra-N-(benzyloxycarbonyl)-5,6-O-cyclohexylideneneamine；1,3,2',6'-Tetra-N-benzyloxycarbonyl-5,6-O-cyclohexyliden-neamin；1,3,2',6'-Tetra-N-benzyloxycarbonyl-5,6-O-cyclohexylidenneamin
• CAS: 55728-75-1
• 化学式: C₅₀H₅₈N₄O₁₄
• 分子量: 939.029
• InChiKey: LWGOUPPSLDYQFU-MOVIIYLLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.48
• 重原子数：
  68.0
• 可旋转键数：
  15.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  230.7
• 氢给体数：
  6.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  1,3,2',6'-tetrakis(N-benzyloxycarbonyl)-5,6-O-cyclohexylideneneamine 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 97.67h， 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：

  neamine tetrahydrochloride 在 碳酸氢钠 、 对甲苯磺酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.33h， 生成 1,3,2',6'-tetrakis(N-benzyloxycarbonyl)-5,6-O-cyclohexylideneneamine
  参考文献：
  名称：

  针对核糖体解码中心设计的螺双环类似物

  摘要：

  模仿氨基糖苷：已开发出一种优化的方法来合成刚性5,6，，6,6和7,6-双环支架，这些支架模仿了核糖体解码中心天然氨基糖苷的许多相互作用。介绍了它们对A位点的结合亲和力以及在体外抑制蛋白质生成的潜力。我们的结果包括针对RNA构建体的基于结构的药物设计的有用SAR观察结果。

  DOI：

  10.1002/cbic.201000591

文献信息

• Total synthesis of neomycin B
  作者：Takayuki Usui、Sumio Umezawa

  DOI：10.1016/0008-6215(88)85087-0

  日期：1988.3

  Abstract Total synthesis of neomycin B, a pseudo-tetrasaccharide aminoglycoside antibiotic, has been achieved through two key glycosylation reactions. Coupling of 3- O -acetyl-2,6-diazido-4- O -benzyl-2,6-dideoxy- l -idopyranosyl chloride with 5- O -benzoyl-1,2- O -isopropylidene-α- d -ribofuranose under modified Koenigs-Knorr conditions gave 70% of the desired β- l disaccharide ( 3 ) corresponding

  摘要已通过两个关键的糖基化反应实现了拟四糖氨基糖苷类抗生素新霉素B的全合成。3-O-乙酰基-2,6-二叠氮基-4-O-苄基-2,6-二脱氧-1-基吡喃糖基氯与5-O-苯甲酰基-1,2-O-异亚丙基-α-d-核呋喃糖的偶联在改良的Koenigs-Knorr条件下，得到70％的所需β-1二糖（3），其对应于结构上的新生物胺。在3的异异丙基化和乙酰化之后，1,2-二-O-乙酰基-3-O-（3-O-乙酰基-2,6-重氮基-4-O-苄基-2,6-二脱氧-β-1-偶氮吡喃基）-5-O-苯甲酰基-d-呋喃呋喃糖与3,2'，6'-三-N-（苄氧基-羰基）-1-N：6-O-羰基-3'的HO-5偶联，使用三甲基甲硅烷基三氟甲磺酸盐制备的4'-二-O-（邻甲氧基苯甲酰基）亚胺，