teicoplanin A₃-1 | 93616-27-4

• 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 A₃-1
• 英文别名: Teicoplanin A3-1；(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-26,31,44,49,64-pentahydroxy-21,35,38,54,56,59-hexaoxo-47-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-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: 93616-27-4
• 化学式: C₇₂H₆₈Cl₂N₈O₂₈
• 分子量: 1564.27
• InChiKey: SUFIXUDUKRJOBH-JSMFNTJWSA-N

物化性质

• 密度：
  1.80±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于乙醇；可溶于甲醇；可溶于DMSO；可溶于二甲基甲酰胺

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  110
• 可旋转键数：
  8
• 环数：
  15.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  574
• 氢给体数：
  21
• 氢受体数：
  29

反应信息

• 作为反应物：
  描述：

  teicoplanin A₃-1 在 sodium tetrahydroborate 、 水 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以75%的产率得到(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-22,34-diamino-5,15-dichloro-26,31,44,49,62-pentahydroxy-19-(hydroxymethyl)-21,35,38,54,56-pentaoxo-47-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-7,13,28-trioxa-20,36,39,53,55-pentazadecacyclo[38.14.2.23,6.214,17.18,12.123,27.129,33.141,45.010,37.046,51]tetrahexaconta-3,5,8,10,12(62),14,16,23(59),24,26,29(58),30,32,41(57),42,44,46(51),47,49,60,63-henicosaene-52-carboxylic acid
  参考文献：
  名称：

  Structural Modifications of the Active Site in Teicoplanin and Related Glycopeptides. 1. Reductive Hydrolysis of the 1,2- and 2,3-Peptide Bonds

  摘要：

  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.

  DOI：

  10.1021/jo941809v
• 作为产物：
  描述：

  teicoplanin A2-2 在 硫酸 作用下， 以 二甲基亚砜 为溶剂， 反应 1.5h， 生成 teicoplanin A₃-1
  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

文献信息

• New semisynthetic teicoplanin derivatives have comparable in vitro activity to that of oritavancin against clinical isolates of VRE
  作者：Zsolt Szűcs、Eszter Ostorházi、Máté Kicsák、Lajos Nagy、Anikó Borbás、Pál Herczegh

  DOI：10.1038/s41429-019-0164-1

  日期：2019.7

  teicoplanin pseudoaglycon derivative have been synthesized with the aim of optimizing the in vitro activity of the compound against VanA type vancomycin resistant enterococci (VRE) isolated from hospitalized patients. Teicoplanin, vancomycin, and oritavancin were used as reference antibiotics for the antibacterial evaluations. One of the new derivatives exhibited far superior activity than the original compound

  合成了十个替考拉宁假糖苷配基衍生物的十个类似物，目的是优化该化合物对分离自住院患者的VanA型耐万古霉素肠球菌（VRE）的体外活性。使用替考拉宁，万古霉素和奥利万星作为参考抗生素进行抗菌评估。一种新的衍生物表现出远优于原始化合物的活性。所测得的体外MIC与奥利万星在所研究的VRE菌株上的MIC相当。
• Synthesis and biological properties of N63-carboxamides of teicoplanin antibiotics. Structure-activity relationships
  作者：Adriano Malabarba、Aldo Trani、Paolo Strazzolini、Giuseppe Cietto、Pietro Ferrari、Giorgio Tarzia、Rosa Pallanza、Marisa Berti

  DOI：10.1021/jm00131a007

  日期：1989.11

  function of teicoplanin A2 (CTA) and its acidic hydrolysis pseudoaglycons (TB, TC) and aglycon (TD) with amines carrying various functional groups and chains produced amide derivatives with different isoelectric points and lipophilicities. Amide formation did not affect the ability of these compounds to bind to Ac2-L-Lys-D-Ala-D-Ala, a model for the natural peptide binding site in bacterial cell walls

  替考拉宁A2（CTA）的羧基官能团及其酸性水解假糖胺（TB，TC）和糖苷配基（TD）与带有各种官能团和链的胺的缩合产生具有不同等电点和亲脂性的酰胺衍生物。酰胺的形成并不影响这些化合物与Ac2-L-Lys-D-Ala-D-Ala结合的能力，Ac2-L-Lys-D-Ala-D-Ala是细菌细胞壁中天然肽结合位点的模型。发现替考拉宁酰胺的抗微生物活性主要取决于它们的离子和亲脂特性以及所存在的糖的类型和数量。带正电荷的酰胺通常比未修饰的针对革兰氏阳性生物的抗生素具有更高的体外活性。特别是，CTA的大多数碱性酰胺对凝结酶阴性葡萄球菌的活性均明显高于替考拉宁。少量的TC酰胺和大多数的TD酰胺对革兰氏阴性菌也显示出一定的活性。在小鼠实验性化脓性链球菌败血症中，皮下给药时，某些碱性酰胺比母体替考拉宁更具活性。通过口服途径，一些CTA也比替考拉宁更有效。
• Reductive Hydrolysis of the 59,60-Amide Bond of Teicoplanin Antibiotics: A Key Step from Natural to Synthetic Glycopeptides
  作者：Adriano Malabarba、Romeo Ciabatti

  DOI：10.1021/jm00045a002

  日期：1994.9
• Coronelli; Gallo; Cavalleri, Farmaco, Edizione Scientifica, 1987, vol. 42, # 10, p. 767 - 786
  作者：Coronelli、Gallo、Cavalleri

  DOI：——

  日期：——
• 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.