(1S,2R,19R,22R,34S,37R,40R,52S)-5,15-dichloro-2,26,31,44,47,49,64-heptahydroxy-22-[(2-methylpropan-2-yl)oxycarbonylamino]-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 | 104581-77-3

• 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: (1S,2R,19R,22R,34S,37R,40R,52S)-5,15-dichloro-2,26,31,44,47,49,64-heptahydroxy-22-[(2-methylpropan-2-yl)oxycarbonylamino]-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: 104581-77-3
• 化学式: C₆₃H₅₃Cl₂N₇O₂₀
• 分子量: 1299.05
• InChiKey: PLVIBWSHKFMVSL-YYMLIVBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  92
• 可旋转键数：
  4
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  420
• 氢给体数：
  15
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  (1S,2R,19R,22R,34S,37R,40R,52S)-5,15-dichloro-2,26,31,44,47,49,64-heptahydroxy-22-[(2-methylpropan-2-yl)oxycarbonylamino]-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 在 sodium tetrahydroborate 、 水 作用下， 以 乙醇 为溶剂， 反应 72.0h， 以5.6 g的产率得到(1S,2R,19R,22S,25R,28R,40S)-19-amino-5,15-dichloro-2,32,35,37,48-pentahydroxy-22-[3-hydroxy-5-[2-hydroxy-5-[(1R)-2-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]phenoxy]phenyl]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8,10,12(48),14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-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：

  二碳酸二叔丁酯 、 替考拉宁 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (1S,2R,19R,22R,34S,37R,40R,52S)-5,15-dichloro-2,26,31,44,47,49,64-heptahydroxy-22-[(2-methylpropan-2-yl)oxycarbonylamino]-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
  参考文献：
  名称：

  替考拉宁苷元衍生物的热阻转异构：通过 DE 环系统的选择性平衡制备替考拉宁苷元的 P、P、PandM、P、PA 转异构体

  摘要：

  详细介绍了替考拉宁降解为一系列关键苷元衍生物，包括那些含有裂解 FG 环系统的衍生物，并对其热阻转异构现象进行了研究。在所有情况下，在 AB 和 CD 阻转异构体立体化学不受影响的条件下，观察到 DE 环系统的选择性平衡以提供 P:M 阻转异构体的 1:1 混合物。发现 DE 阻转异构体平衡发生时，6a（完整 FG 环系统）和 10/12（裂解 FG 环系统）的 Ea 分别为 29.3 和 24.8-25.2 kcal/mol，与万古霉素苷元相当DE 环系统 (Ea = 23.6 kcal/mol) 并且比 CD (Ea = 30.4 kcal/mol) 或 O-甲基化 AB 环系统 (Ea = 37.8 kcal/mol) 更容易。符合直觉预期，完整的替考拉宁 FG 环系统减慢了异构化的速度，贡献了大约。Ea 为 4.0 kcal/mol（6a 对 10），替考拉宁无环 FG 衍生物上庞大的

  DOI：

  10.1021/ja002376i

文献信息

• 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。
• MALABARBA, ADRIANO;FERRARI, PIETRO;CIETTO, GIUSEPPE;PALLANZA, ROSA;BERTI,+, J. ANTIBIOTICS, 42,(1989) N2, C. 1800-1816
  作者：MALABARBA, ADRIANO、FERRARI, PIETRO、CIETTO, GIUSEPPE、PALLANZA, ROSA、BERTI,+

  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.
• Thermal Atropisomerism of Teicoplanin Aglycon Derivatives:  Preparation of the <i>P</i>,<i>P</i>,<i>P</i> and <i>M</i>,<i>P</i>,<i>P</i> Atropisomers of the Teicoplanin Aglycon via Selective Equilibration of the DE Ring System
  作者：Dale L. Boger、Jian-Hui Weng、Susumu Miyazaki、J. Jeffrey McAtee、Steven L. Castle、Seong Heon Kim、Yoshiki Mori、Olivier Rogel、Harald Strittmatter、Qing Jin

  DOI：10.1021/ja002376i

  日期：2000.10.1

  a series of key aglycon derivatives, including those containing a cleaved FG ring system, and a study of their thermal atropisomerism are detailed. In all cases, selective equilibration of the DE ring system was observed to provide a 1:1 mixture of P:M atropisomers under conditions in which the AB and CD atropisomer stereochemistry were unaffected. The DE atropisomer equilibration was found to occur

  详细介绍了替考拉宁降解为一系列关键苷元衍生物，包括那些含有裂解 FG 环系统的衍生物，并对其热阻转异构现象进行了研究。在所有情况下，在 AB 和 CD 阻转异构体立体化学不受影响的条件下，观察到 DE 环系统的选择性平衡以提供 P:M 阻转异构体的 1:1 混合物。发现 DE 阻转异构体平衡发生时，6a（完整 FG 环系统）和 10/12（裂解 FG 环系统）的 Ea 分别为 29.3 和 24.8-25.2 kcal/mol，与万古霉素苷元相当DE 环系统 (Ea = 23.6 kcal/mol) 并且比 CD (Ea = 30.4 kcal/mol) 或 O-甲基化 AB 环系统 (Ea = 37.8 kcal/mol) 更容易。符合直觉预期，完整的替考拉宁 FG 环系统减慢了异构化的速度，贡献了大约。Ea 为 4.0 kcal/mol（6a 对 10），替考拉宁无环 FG 衍生物上庞大的