N-acetylglucosaminyl teicoplanin aglycon

• 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: N-acetylglucosaminyl teicoplanin aglycon
• 英文别名: (1S,2R,19R,22R,34S,37R,40R,52R)-2-[(2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-amino-5,15-dichloro-26,31,44,47,49,64-hexahydroxy-21,35,38,54,56,59-hexaoxo-7,13,28-trioxa-20,36,39,53,55,58-hexazaundecacyclo[38.14.2.23,6.214,17.219,34.18,12.123,27.129,33.141,45.010,37.046,51]hexahexaconta-3,5,8,10,12(64),14,16,23(61),24,26,29(60),30,32,41(57),42,44,46(51),47,49,62,65-henicosaene-52-carboxylic acid
• 化学式: C₆₆H₅₈Cl₂N₈O₂₃
• 分子量: 1402.13
• InChiKey: QQVNVTUTURPJSE-YHJKGPFESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  99
• 可旋转键数：
  5
• 环数：
  14.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  495
• 氢给体数：
  18
• 氢受体数：
  24

反应信息

• 作为反应物：
  描述：

  N-acetylglucosaminyl teicoplanin aglycon 在 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 以72%的产率得到
  参考文献：
  名称：

  A few atoms make the difference: Synthetic, CD, NMR and computational studies on antiviral and antibacterial activities of glycopeptide antibiotic aglycon derivatives

  摘要：

  Despite the close structural similarity between the heptapeptide cores of the glycopeptide antibiotics teicoplanin and ristocetin, synthetically modified derivatives of their aglycons show significantly different antibacterial and antiviral properties. The teicoplanin aglycon derivatives with one exception proved to be potent antibacterials but they did not exhibit anti-influenza virus activity. In contrast, the aglycoristocetin derivatives generally showed high anti-influenza virus activity and possessed moderate antibacterial activity. A systematic structure-activity relationship study has been carried out on ristocetin and teicoplanin aglycon derivatives, to explore which structural differences are responsible for these markedly different biological activities. According to electronic circular dichroism and in silica conformational studies, it was found that the differences in anti-influenza virus activity are mainly determined by the conformation of the heptapeptide core of the antibiotics controlled by the presence or absence of chloro substituents. Knowledge of the bioactive conformation will help to design new analogs with improved anti-influenza virus activity. For the teicoplanin derivatives, it was shown that derivatization to improve the antiviral efficacy was accompanied by a significant decrease in antibacterial activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.02.028
• 作为产物：
  描述：

  teicoplanin A2-2 在 氢氟酸 、 苯甲醚 作用下， 反应 2.0h， 以80%的产率得到N-acetylglucosaminyl teicoplanin aglycon
  参考文献：
  名称：

  替考拉宁伪糖苷的异吲哚和苯并异吲哚衍生物的合成具有显着的抗菌和抗病毒活性

  摘要：

  在与邻苯二甲醛或萘-2,3-二卡甲醛和各种硫醇的反应中，替考拉宁假糖苷配基的主要氨基官能团已转化为芳基硫代异吲哚或苯并异吲哚和糖基硫代异吲哚衍生物。在ng / ml浓度范围内，所有获得的半合成抗生素均对革兰氏阳性细菌表现出有效的抗菌活性。其中一些显示出抗病毒活性，特别是针对流感病毒。

  DOI：

  10.1016/j.bmcl.2012.09.079

文献信息

• Lipophilic teicoplanin pseudoaglycon derivatives are active against vancomycin- and teicoplanin-resistant enterococci
  作者：Zsolt Szűcs、Ilona Bereczki、Magdolna Csávás、Erzsébet Rőth、Anikó Borbás、Gyula Batta、Eszter Ostorházi、Réka Szatmári、Pál Herczegh

  DOI：10.1038/ja.2017.2

  日期：2017.5

  A selection of nine derivatives of teicoplanin pseudoaglycon were tested in vitro against clinical vancomycin-resistant Enterococcus strains possessing vanA, vanB or both genes. The bacteria were characterized by PCR for the identification of their resistance genes. The tested compounds contain lipoic acid, different carbohydrates and aryl groups as lipophilic moieties. About one-third of the teicoplanin-resistant

  在体外针对具有vanA，vanB或两个基因的临床耐万古霉素肠球菌菌株测试了teicoplanin伪糖苷配基的9种衍生物。通过PCR表征细菌以鉴定其抗性基因。所测试的化合物包含硫辛酸，不同的碳水化合物和芳基作为亲脂性部分。已显示约三分之一的替考拉宁抗性菌株对一种或多种糖肽衍生物敏感。
• Synthesis of isoindole and benzoisoindole derivatives of teicoplanin pseudoaglycon with remarkable antibacterial and antiviral activities
  作者：Attila Sipos、Zsolt Török、Erzsébet Rőth、Attila Kiss-Szikszai、Gyula Batta、Ilona Bereczki、Zsolt Fejes、Anikó Borbás、Eszter Ostorházi、Ferenc Rozgonyi、Lieve Naesens、Pál Herczegh

  DOI：10.1016/j.bmcl.2012.09.079

  日期：2012.12

  The primary amino function of teicoplanin pseudoaglycon has been transformed into arylthioisoindole or benzoisoindole and glycosylthioisoindole derivatives, in a reaction with o-phthalaldehyde or naphtalene-2,3-dicarbaldehyde and various thiols. All of the obtained semisynthetic antibiotics exhibited potent antibacterial activities against Gram-positive bacteria in the ng per ml concentration range

  在与邻苯二甲醛或萘-2,3-二卡甲醛和各种硫醇的反应中，替考拉宁假糖苷配基的主要氨基官能团已转化为芳基硫代异吲哚或苯并异吲哚和糖基硫代异吲哚衍生物。在ng / ml浓度范围内，所有获得的半合成抗生素均对革兰氏阳性细菌表现出有效的抗菌活性。其中一些显示出抗病毒活性，特别是针对流感病毒。
• A few atoms make the difference: Synthetic, CD, NMR and computational studies on antiviral and antibacterial activities of glycopeptide antibiotic aglycon derivatives
  作者：Ilona Bereczki、Attila Mándi、Erzsébet Rőth、Anikó Borbás、Ádám Fizil、István Komáromi、Attila Sipos、Tibor Kurtán、Gyula Batta、Eszter Ostorházi、Ferenc Rozgonyi、Evelien Vanderlinden、Lieve Naesens、Ferenc Sztaricskai、Pál Herczegh

  DOI：10.1016/j.ejmech.2015.02.028

  日期：2015.4

  Despite the close structural similarity between the heptapeptide cores of the glycopeptide antibiotics teicoplanin and ristocetin, synthetically modified derivatives of their aglycons show significantly different antibacterial and antiviral properties. The teicoplanin aglycon derivatives with one exception proved to be potent antibacterials but they did not exhibit anti-influenza virus activity. In contrast, the aglycoristocetin derivatives generally showed high anti-influenza virus activity and possessed moderate antibacterial activity. A systematic structure-activity relationship study has been carried out on ristocetin and teicoplanin aglycon derivatives, to explore which structural differences are responsible for these markedly different biological activities. According to electronic circular dichroism and in silica conformational studies, it was found that the differences in anti-influenza virus activity are mainly determined by the conformation of the heptapeptide core of the antibiotics controlled by the presence or absence of chloro substituents. Knowledge of the bioactive conformation will help to design new analogs with improved anti-influenza virus activity. For the teicoplanin derivatives, it was shown that derivatization to improve the antiviral efficacy was accompanied by a significant decrease in antibacterial activity. (C) 2015 Elsevier Masson SAS. All rights reserved.