Hexa-N-(benzyloxycarbonyl)neomycin B | 58096-78-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Hexa-N-(benzyloxycarbonyl)neomycin B
• 英文别名: benzyl N-[(1S,2R,3R,4S,5R)-2-[(2R,3R,4R,5S,6R)-4,5-dihydroxy-3-(phenylmethoxycarbonylamino)-6-(phenylmethoxycarbonylaminomethyl)oxan-2-yl]oxy-3-[(2S,3R,4S,5R)-4-[(2R,3R,4R,5S,6S)-4,5-dihydroxy-3-(phenylmethoxycarbonylamino)-6-(phenylmethoxycarbonylaminomethyl)oxan-2-yl]oxy-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4-hydroxy-5-(phenylmethoxycarbonylamino)cyclohexyl]carbamate
• CAS: 58096-78-9
• 化学式: C₇₁H₈₂N₆O₂₅
• 分子量: 1419.46
• InChiKey: MYNBJDDXTICSHS-WPOGQAPLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  102
• 可旋转键数：
  33
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  427
• 氢给体数：
  13
• 氢受体数：
  25

反应信息

• 作为反应物：
  描述：

  Hexa-N-(benzyloxycarbonyl)neomycin B 在 [(2,9-dimethyl-1,10-phenanthroline)-Pd(μ-OAc)]₂(OTf)₂ 、 水 作用下， 以 二甲基亚砜 为溶剂， 反应 20.0h， 以41%的产率得到
  参考文献：
  名称：

  氨基糖苷类抗生素的后期修饰克服了 APH(3') 激酶介导的细菌耐药性。

  摘要：

  抗菌药物耐药性的不断出现正在对多重耐药病原体感染的患者造成威胁。特别是作为最后手段的广谱抗菌药物氨基糖苷类抗生素的临床使用由于细菌耐药性的上升而受到限制。革兰氏阳性和革兰氏阴性细菌的主要耐药机制之一是 O-磷酸转移酶 [APH(3')s] 在 3' 位磷酸化这些氨基糖。改变这些抗生素 3' 位的结构将是解决这种耐药机制的明显策略。然而，获得此类衍生物需要繁琐的多步合成，这对于这个低投资回报市场的制药行业来说并不有吸引力。为了克服这一障碍并对抗 APH(3') 介导的细菌耐药性，我们通过钯催化氧化在 3' 位引入了氨基糖苷类的新型区域选择性修饰。为了强调我们的氨基糖苷类结构修饰方法的有效性，我们开发了两种新型候选抗生素，仅采用四个合成步骤即可克服 APH(3')s 介导的耐药性。

  DOI：

  10.1002/chem.202200883
• 作为产物：
  描述：

  苯甲氧羰酰琥珀酰亚胺 、 硫酸新霉素 在 potassium carbonate 、 N,N-二甲基-1,3-二氨基丙烷 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 18.0h， 以93%的产率得到Hexa-N-(benzyloxycarbonyl)neomycin B
  参考文献：
  名称：

  [EN] ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
  [FR] ANALOGUES D'AMINOGLYCOSIDE ANTIBACTÉRIENS

  摘要：

  公开号：

  WO2011044538A9

文献信息

• Toward Overcoming <i>Staphylococcus aureus</i> Aminoglycoside Resistance Mechanisms with a Functionally Designed Neomycin Analogue
  作者：Stephen Hanessian、Alexandre Giguère、Justyna Grzyb、Juan Pablo Maianti、Oscar M. Saavedra、James B. Aggen、Martin S. Linsell、Adam A. Goldblum、Darin J. Hildebrandt、Timothy R. Kane、Paola Dozzo、Micah J. Gliedt、Rowena D. Matias、Lee Ann Feeney、Eliana S. Armstrong

  DOI：10.1021/ml200202y

  日期：2011.12.8

  introduction of an N1-(l)-HABA group in the 2-deoxystreptamine subunit (ring B) leads to a novel and potent antibiotic (1) with activity against strains of S. aureus carrying known aminoglycoside resistance determinants, as well as against an extended panel of Methicillin-resistant S. aureus isolates (n = 50). Antibiotic 1 displayed >64 fold improvement in MIC50 and MIC90 against this MRSA collection

  新霉素A和D环中的二醇基团脱氧，并在2-脱氧链胺基亚基（环B）中引入N1-（l）-HABA基团，产生了一种新型且有效的抗生素（1）带有已知氨基糖苷抗性决定簇的金黄色葡萄球菌菌株，以及针对耐甲氧西林的金黄色葡萄球菌分离株的扩展面板（n = 50）。与临床相关的氨基糖苷类阿米卡星和庆大霉素相比，抗生素1相对于该MRSA集合在MIC50和MIC90中显示出> 64倍的改善。合成是通过六个步骤完成的，总产率为15％。
• [EN] SELECTIVE OXIDATION OF CARBOHYDRATES<br/>[FR] OXYDATION SÉLECTIVE DES GLUCIDES
  申请人：UNIV GRONINGEN

  公开号：WO2013191549A1

  公开（公告）日：2013-12-27

  The invention relates to the field of carbohydrate chemistry. Provided is a process for the regioselective oxidation of a single secondary hydroxy function of a carbohydrate substrate comprising two or more secondary hydroxy functions, comprising contacting the carbohydrate substrate in a solvent in the presence of a transition metal catalyst complex with an oxidizing agent to yield a mono-oxidized carbohydrate.

  该发明涉及碳水化合物化学领域。提供了一种用于对碳水化合物底物中的单个次生羟基功能进行区域选择氧化的方法，该底物包含两个或更多个次生羟基功能，包括将碳水化合物底物在溶剂中与过渡金属催化剂复合物和氧化剂接触以产生单氧化的碳水化合物。
• Aminoglycoside antibiotics. 4. Regiospecific partial synthesis of ribostamycin and 4"-thioribostamycin
  作者：Virendra Kumar、William A. Remers

  DOI：10.1021/jo00334a042

  日期：1981.10
• Selective Inhibition of Bacterial and Human Topoisomerases by <i>N</i>-Arylacyl <i>O</i>-Sulfonated Aminoglycoside Derivatives
  作者：Amanda M. Fenner、Lisa M. Oppegard、Hiroshi Hiasa、Robert J. Kerns

  DOI：10.1021/ml3004507

  日期：2013.5.9

  Numerous therapeutic applications have been proposed for molecules that bind heparin-binding proteins. Development of such compounds has primarily focused on optimizing the degree and orientation of anionic groups on a scaffold, but utility of these polyanions has been diminished by their typically large size and nonspecific interactions with many proteins. In this study, N-arylacyl O-sulfonated aminoglycosides were synthesized and evaluated for their ability to selectively inhibit structurally similar bacterial and human topoisomerases. It is demonstrated that the structure of the aminoglycoside and of the N-arylacyl moiety imparts selective inhibition of different topoisomerases and alters the mechanism. The results here outline a strategy that will be applicable to identifying small, structurally defined oligosaccharides that bind heparin-binding proteins with a high degree of selectivity.
• Exploring the Use of Conformationally Locked Aminoglycosides as a New Strategy to Overcome Bacterial Resistance
  作者：Agatha Bastida、Ana Hidalgo、Jose Luis Chiara、Mario Torrado、Francisco Corzana、Jose Manuel Pérez-Cañadillas、Patrick Groves、Eduardo Garcia-Junceda、Carlos Gonzalez、Jesús Jimenez-Barbero、Juan Luis Asensio

  DOI：10.1021/ja0543144

  日期：2006.1.1

  The emergence of bacterial resistance to the major classes of antibiotics has become a serious problem over recent years. For aminoglycosides, the major biochemical mechanism for bacterial resistance is the enzymatic modification of the drug. Interestingly, in several cases, the oligosaccharide conformation recognized by the ribosomic RNA and the enzymes responsible for the antibiotic inactivation is remarkably different. This observation suggests a possible structure-based chemical strategy to overcome bacterial resistance; in principle, it should be possible to design a conformationally locked oligosaccharide that still retains antibiotic activity but that is not susceptible to enzymatic inactivation. To explore the scope and limitations of this strategy, we have synthesized several aminoglycoside derivatives locked in the ribosome-bound "bioactive" conformation. The effect of the structural preorganization on RNA binding, together with its influence on the aminoglycoside inactivation by several enzymes involved in bacterial resistance, has been studied. Our results indicate that the conformational constraint has a modest effect on their interaction with ribosomal RNA. In contrast, it may display a large impact on their enzymatic inactivation. Thus, the work presented herein provides a key example of how the conformational differences exhibited by these ligands within the binding pockets of the ribosome and of those enzymes involved in bacterial resistance can, in favorable cases, be exploited for designing new antibiotic derivatives with improved activity in resistant strains.