tetra-N-(benzyloxycarbonyl)neamine | 22854-75-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tetra-N-(benzyloxycarbonyl)neamine
• 英文别名: benzyl N-[(2R,3R,4R,5S,6R)-2-[(1R,2R,3S,4R,6S)-2,3-dihydroxy-4,6-bis(phenylmethoxycarbonylamino)cyclohexyl]oxy-4,5-dihydroxy-6-(phenylmethoxycarbonylaminomethyl)oxan-3-yl]carbamate
• CAS: 22854-75-7
• 化学式: C₄₄H₅₀N₄O₁₄
• 分子量: 858.899
• InChiKey: XMQWDKPZQQFYEW-AFFUZZABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  62
• 可旋转键数：
  19
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  253
• 氢给体数：
  8
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  tetra-N-(benzyloxycarbonyl)neamine 生成 benzyl N-[(2R,3R,4R,5S,6R)-2-[(3aR,4R,5S,7R,7aR)-5,7-bis(phenylmethoxycarbonylamino)spiro[3a,4,5,6,7,7a-hexahydro-1,3-benzodioxole-2,1'-cyclohexane]-4-yl]oxy-4,5-dihydroxy-6-(phenylmethoxycarbonylaminomethyl)oxan-3-yl]carbamate
  参考文献：
  名称：

  USUI, TAKAYUKI;UMEZAWA, SUMIO, J. ANTIBIOTICS, 40,(1987) N 10, 1464-1467

  摘要：

  DOI：
• 作为产物：
  描述：

  neomycin B x sulfate 在 盐酸 、 碳酸氢钠 作用下， 以 甲醇 、 水 为溶剂， 反应 22.33h， 生成 tetra-N-(benzyloxycarbonyl)neamine
  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

• Rapid Combinatorial Synthesis of Aminoglycoside Antibiotic Mimetics:  Use of a Polyethylene Glycol-Linked Amine and a Neamine-Derived Aldehyde in Multiple Component Condensation as a Strategy for the Discovery of New Inhibitors of the HIV RNA Rev Responsive Element
  作者：William K. C. Park、Manfred Auer、Herbert Jaksche、Chi-Huey Wong

  DOI：10.1021/ja9612817

  日期：1996.1.1

  A library of neomycin B mimetics has been prepared rapidly without chromatography using a neamine-derived aldehyde, tert-butyl isocyanide or isocyanoacetic acid methyl ester, a glycine-conjugated polyethylene glycol (PEG) methyl ether, and various Cbz-N-protected amino acids as substrates in a Ugi-type one-pot reaction. The product linked to PEG was isolated by precipitation in ether. A simultaneous

  使用新霉素衍生的醛、叔丁基异氰化物或异氰乙酸甲酯、甘氨酸缀合的聚乙二醇 (PEG) 甲基醚和各种 Cbz-N 保护的氨基酸，无需色谱法即可快速制备新霉素 B 模拟物文库作为 Ugi 型一锅反应的底物。通过在乙醚中沉淀分离与PEG连接的产物。同时进行碱催化水解和脱氧乙酰化，然后进行氢化，可以轻松访问新霉素 B 模拟物库，该库已筛选与 HIV mRNA (RRE) 的 Rev 响应元件结合。发现一些产品比尼胺活性更高，IC50 值在微摩尔范围内。
• 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，
• Design of Novel Antibiotics that Bind to the Ribosomal Acyltransfer Site
  作者：Jalal Haddad、Lakshmi P. Kotra、Beatriz Llano-Sotelo、Choonkeun Kim、Eduardo F. Azucena、Meizheng Liu、Sergei B. Vakulenko、Christine S. Chow、Shahriar Mobashery

  DOI：10.1021/ja011695m

  日期：2002.4.1

  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.
• Aminoglycoside antibiotics. 1. Regiospecific partial syntheses of ribostamycin and butirosin B
  作者：Virendra Kumar、William A. Remers

  DOI：10.1021/jo00411a014

  日期：1978.8
• Regioselective modification of amino groups in aminoglycosides based on cyclic carbamate formation
  作者：Guihui Chen、Pan Pan、Yun Yao、Ying Chen、Xiangbao Meng、Zhongjun Li

  DOI：10.1016/j.tet.2008.07.022

  日期：2008.9

  Conditions for regioselective introduction of cyclic carbamate into per-N-Cbz neamine and per-N-Cbz kanamycin A have been found. The position and number of cyclic Carbamate formed in these two aminoglycosides was controllable. On the base of selective cyclic carbamate formation, regioselective modification on N-1, N-6' or both amino groups in neat-nine, and on N-6', N-3 '' or both amino groups in kanamycin A was achieved by ring-opening reaction with amines. A new neamine dimer linked at the N-1 was also synthesized with this method. (C) 2008 Elsevier Ltd. All rights reserved.