teicoplanin pseudoaglycone | 91032-39-2

• 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: teicoplanin pseudoaglycone
• 英文别名: (1S,2R,19R,22R,34S,37R,40R,52S)-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
• CAS: 91032-39-2
• 化学式: C₆₆H₅₈Cl₂N₈O₂₃
• 分子量: 1402.13
• InChiKey: QQVNVTUTURPJSE-PQTDOWIESA-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：

  teicoplanin pseudoaglycone 在 硫酸 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 以1.82%的产率得到替考拉宁
  参考文献：
  名称：

  在基于替考拉宁的LC固定相上，碳水化合物部分在手性识别中的作用。

  摘要：

  在这项研究中，我们使用了大环抗生素替考拉宁，该分子由糖苷配基肽“篮子”和三个附着的碳水化合物（糖）部分组成。除去糖单元并纯化糖苷配基。以相似的方式制备了两个手性固定相（CSP），一个带有天然替考拉宁分子，另一个带有糖苷配基。在具有七个RPLC流动相和两个极性有机流动相的两个CSP上评估了26种化合物。这些化合物是13种氨基酸或与结构相关的化合物（包括DOPA，亚叶酸等）和其他13种化合物（例如肉碱，溴苯甲酰胺等）。色谱结果以保留，选择性，和分离因子，以及对应于两种对映异构体分离的峰效率和对映选择性自由能差。两个CSP的极性相似。已经清楚地确定，糖苷配基负责氨基酸的对映体分离。对于氨基酸对映体分离，糖苷配基CSP和替考拉宁CSP之间的对映选择性自由能之差在0.3和1 kcal / mol之间。与糖苷配基CSP相比，分离度提高了2-5倍。仅在替考拉宁CSP上分离了四种非氨基酸化合物。在替考拉宁

  DOI：

  10.1021/ac991004t
• 作为产物：
  描述：

  teicoplanin A2-2 在 氢氟酸 作用下， 以 苯甲醚 为溶剂， 反应 2.0h， 以80%的产率得到teicoplanin pseudoaglycone
  参考文献：
  名称：

  Diazo Transfer−Click Reaction Route to New, Lipophilic Teicoplanin and Ristocetin Aglycon Derivatives with High Antibacterial and Anti-influenza Virus Activity: An Aggregation and Receptor Binding Study

  摘要：

  Semisynthetic, lipophilic ristocetin and teicoplanin derivatives were prepared starting from ristocetin aglycon and teicoplanin psi-aglycon (N-acetyl-D-glucosaminyl aglycoteicoplanin). The terminal amino functions of the aglycons were converted into azido form by triflic azide. Copper catalyzed 1,3-dipolar cycloaddition reaction with lipophilic alkynes resulted in the title compounds. Two of the teicoplanin derivatives showed very good MIC and MBC values against various Gram-positive bacteria, including vanA enterococci. The aggregation and interaction of a n-decyl derivative with bacterial cell wall components Was Studied. One of the lipophilic ristocetin derivatives displayed favorable anti-influenza virus activity.

  DOI：

  10.1021/jm900950d

文献信息

• Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication
  作者：Ilona Bereczki、Henrietta Papp、Anett Kuczmog、Mónika Madai、Veronika Nagy、Attila Agócs、Gyula Batta、Márton Milánkovits、Eszter Ostorházi、Ana Mitrović、Janko Kos、Áron Zsigmond、István Hajdú、Zsolt Lőrincz、Dávid Bajusz、György Miklós Keserű、Jan Hodek、Jan Weber、Ferenc Jakab、Pál Herczegh、Anikó Borbás

  DOI：10.3390/ph14111111

  日期：——

  development of new drugs against the causative agent SARS-CoV-2. The clinically used glycopeptide antibiotic, teicoplanin, emerged as a potential antiviral, and its efficacy was improved with lipophilic modifications. This prompted us to prepare new lipophilic apocarotenoid conjugates of teicoplanin, its pseudoaglycone and the related ristocetin aglycone. Their antiviral effect was tested against SARS-CoV-2

  旷日持久的全球 COVID-19 大流行促使开发针对病原体 SARS-CoV-2 的新药。临床上使用的糖肽类抗生素替考拉宁成为一种潜在的抗病毒药物，并且通过亲脂性修饰提高了其疗效。这促使我们制备替考拉宁、其假糖苷配基和相关瑞斯托霉素糖苷配基的新型亲脂性类胡萝卜素缀合物。使用细胞活力测定和病毒 RNA 的定量 PCR 在 Vero E6 细胞中测试了它们对 SARS-CoV-2 的抗病毒作用，证实了它们对病毒复制的微摩尔抑制活性。有趣的是，母体类胡萝卜素中的两种，bixin 和 β-apo-8'胡萝卜素酸，发挥了显着的抗 SARS-CoV-2 活性。机制研究涉及组织蛋白酶 L 和 B，以及主要蛋白酶 3CLPro，并且通过计算研究使结果合理化。糖肽缀合物显示双重抑制作用，而类胡萝卜素主要具有组织蛋白酶 B 和 L 亲和力。由于替考拉宁是一种上市抗生素，而天然碧玺是一种经批准、廉价且广泛使用的
• N-Terminal guanidine derivatives of teicoplanin antibiotics strongly active against glycopeptide resistant Enterococcus faecium
  作者：Zsolt Szűcs、Ilona Bereczki、Erzsébet Rőth、Márton Milánkovits、Eszter Ostorházi、Gyula Batta、Lajos Nagy、Zsuzsanna Dombrádi、Anikó Borbás、Pál Herczegh

  DOI：10.1038/s41429-020-0313-6

  日期：2020.9

  Antibiotic resistance is one of the major challenges in healthcare of our time. To meet this challenge, we designed and prepared guanidine and lipophilic guanidine derivatives of the glycopeptide antibiotic teicoplanin to armed them with activity against the most threatening nosocomial bacteria, multiresistant enterococci. From teicoplanin and its pseudoaglycone, a series of N-terminal guanidine derivatives

  抗生素耐药性是当今时代医疗保健的主要挑战之一。为了应对这一挑战，我们设计并制备了糖肽抗生素替考拉宁的胍和亲脂胍衍生物，使其具有抵抗最具威胁性的医院细菌多耐药肠球菌的活性。由替考拉宁及其假糖苷配基制备了具有游离和酰胺C端部分的一系列N端胍衍生物。制备了六个脂族和芳族亲脂性碳二亚胺，并用于合成亲脂性胍替考拉宁缀合物。所有新的N末端胍类抗生素均对标准的革兰氏阳性菌显示出高活性。四个选定的衍生物显示出对一系列院内VanA肠球菌粪便菌株的优异抗菌活性。
• The First Dimeric Derivatives of the Glycopeptide Antibiotic Teicoplanin
  作者：Ilona Bereczki、Zsolt Szűcs、Gyula Batta、Tamás Milán Nagy、Eszter Ostorházi、Katalin E. Kövér、Anikó Borbás、Pál Herczegh

  DOI：10.3390/ph15010077

  日期：——

  Various dimeric derivatives of the glycopeptide antibiotic teicoplanin were prepared with the aim of increasing the activity of the parent compound against glycopeptide-resistant bacteria, primarily vancomycin-resistant enterococci. Starting from teicoplanin, four covalent dimers were prepared in two orientations, using an α,ω-bis-isothiocyanate linker. Formation of a dimeric cobalt coordination complex

  制备了糖肽抗生素替考拉宁的各种二聚体衍生物，目的是提高母体化合物对糖肽抗性细菌（主要是万古霉素抗性肠球菌）的活性。从替考拉宁开始，使用 α,ω-双-异硫氰酸酯接头在两个方向上制备了四个共价二聚体。已检测到替考拉宁假糖苷配基的 N-末端 L-组氨酰衍生物形成二聚钴配位复合物，并评估了其抗菌活性。通过 DOSY 实验证明了 Co(III) 诱导的组氨酰衍生物二聚化。共价和复合二聚体衍生物均显示出对 VanA 替考拉宁耐药肠球菌的高活性，
• Two Novel Semisynthetic Lipoglycopeptides Active against Staphylococcus aureus Biofilms and Cells in Late Stationary Growth Phase
  作者：Vladimir Vimberg、Leona Zieglerova、Aninda Mazumdar、Zsolt Szűcs、Aniko Borbás、Pál Herczegh、Gabriela Balikova Novotna

  DOI：10.3390/ph14111182

  日期：——

  The increase in antibiotic resistance among Gram-positive bacteria underscores the urgent need to develop new antibiotics. New antibiotics should target actively growing susceptible bacteria that are resistant to clinically accepted antibiotics including bacteria that are not growing or are protected in a biofilm environment. In this paper, we compare the in vitro activities of two new semisynthetic glycopeptide antibiotics, MA79 and ERJ390, with two clinically used glycopeptide antibiotics—vancomycin and teicoplanin. The new antibiotics effectively killed not only exponentially growing cells of Staphylococcus aureus, but also cells in the stationary growth phase and biofilm.

  革兰氏阳性细菌抗生素耐药性的增加强调了开发新抗生素的紧迫性。新的抗生素应该针对活跃生长且对临床接受的抗生素产生抗性的细菌，包括在生物膜环境中不生长或受保护的细菌。在本文中，我们比较了两种新的半合成糖肽类抗生素MA79和ERJ390与两种临床使用的糖肽类抗生素万古霉素和替考普兰在体外活性的差异。新的抗生素不仅有效地杀死了金黄色葡萄球菌的指数生长细胞，还能杀死停滞生长期和生物膜中的细胞。
• Structural Modifications of the Active Site in Teicoplanin and Related Glycopeptides. 1. Reductive Hydrolysis of the 1,2- and 2,3-Peptide Bonds
  作者：Adriano Malabarba、Romeo Ciabatti、Jürgen Kettenring、Pietro Ferrari、Károly Vékey、Elvio Bellasio、Maurizio Denaro

  DOI：10.1021/jo941809v

  日期：1996.1.1

  Reaction of teicoplanin glycopeptides with sodium borohydride in aqueous ethanol solutions produced open pentapeptide derivatives in which the amide bond between amino acids 2 and 3 was hydrolyzed and the carboxyl group of amino acid 2 was reduced to a primary alcohol. Other glycopeptides of the dalbaheptide family, such as vancomycin, ristocetin, and A-40,926, underwent selective reductive hydrolysis (RH) of the heptapeptide backbone at the same position as in teicoplanins, while antibiotic A-42,867 and vancomycin hexapeptide were resistant. Also, teicoplanin and vancomycin were resistant to RH-treatment when the N-terminus was protected as carbamate. In contrast, open hexapeptides in which the 1,2-peptide bond was hydrolyzed and the carboxyl group of amino acid 1 was reduced to hydroxymethyl were obtained from carbamate derivatives of sugar-free compounds deglucoteicoplanin (TD) and vancomycin-aglycon (VA) under RH-conditions. Limited to BOC or CBZ-TD, the 3,4-amide bond was also affected. A possible RH-mechanism is proposed for natural glycopeptides and their derivatives. Teicoplanin-derived RH penta- and hexapeptides maintained residual antibacterial activity. As other analogous RH-glycopeptides, they are key intermediates for the synthesis of new members of this family of antibiotics. A synthetic approach to ring-closed derivatives of TD hexapeptide alcohol (TDHPA) and their activities are also reported.