N-Des-leucylvancomycin aglycone | 115220-79-6

• 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-Des-leucylvancomycin aglycone
• 英文别名: Des-leucylaglycovancomycin；Des(D-MeLeu)-vancomycin aglycon；(1S,2R,18R,19R,22S,25R,28R,40S)-19-amino-22-(2-amino-2-oxoethyl)-5,15-dichloro-2,18,32,35,37,48-hexahydroxy-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
• CAS: 115220-79-6
• 化学式: C₄₆H₃₉Cl₂N₇O₁₆
• 分子量: 1016.76
• InChiKey: KHGMBDIMFQFZDJ-VEAGTWJTSA-N

物化性质

• 沸点：
  1579.1±65.0 °C(predicted)
• 密度：
  1.551±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  71
• 可旋转键数：
  3
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  392
• 氢给体数：
  14
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  N-Des-leucylvancomycin aglycone 在 copper(ll) sulfate pentahydrate 、 triflic azide 、 三乙胺 作用下， 以 吡啶 为溶剂， 反应 12.0h， 以70%的产率得到
  参考文献：
  名称：

  重新编程的抗菌药物万古霉素导致缺乏抗菌活性的有效抗病毒药

  摘要：

  甲型和乙型流感病毒是对人类健康的全球威胁，对现有抗病毒药物的耐药性不断增强，因此有必要提出新的概念来扩大治疗选择范围。糖肽衍生物已经成为有前途的新型抗病毒剂。为了避免潜在的抗生素抗性，这些抗病毒糖肽优选地没有抗生素活性。我们制备了六种万古霉素糖苷配基六肽衍生物，目的是获得具有抗流感病毒但无抗菌活性的化合物。其中两个对甲型和乙型流感病毒的复制产生了强大的选择性抑制作用，同时通过去除关键的N端部分成功消除了抗菌活性。此外，这两种分子还可以抵抗其他几种病毒，例如单纯疱疹病毒，

  DOI：

  10.3390/ph13070139
• 作为产物：
  描述：

  去甲糖胺基万古霉素 在 sodium hydroxide 、 硫代异氰酸苯酯 、 三氟乙酸 作用下， 以 吡啶 、 水 为溶剂， 反应 5.0h， 生成 N-Des-leucylvancomycin aglycone
  参考文献：
  名称：

  从万古霉素和相关抗生素中选择性裂解凡可可胺，葡萄糖和N-甲基亮氨酸

  摘要：

  万古霉素和相关抗生素与三氟乙酸在–15°C的条件下反应40小时，可选择性裂解氨基糖类香豆素。通过与三氟乙酸在50°C下反应3小时，除去第二个糖（葡萄糖），并使用Edman降解程序裂解N末端亮氨酸部分。

  DOI：

  10.1039/c39880001306

文献信息

• Attempted introduction of a fourth amide NH into the carboxylate-binding pocket of glycopeptide antibiotics
  作者：Jochen Görlitzer、Thomas F. Gale、Dudley H. Williams

  DOI：10.1039/a906502d

  日期：——

  We report the synthesis of a novel derivative of the glycopeptide antibiotic vancomycin, modified at the N-terminus. This incorporates a fourth amide NH into the antibiotic, at the position which was formerly the N-terminus of the antibiotic-binding pocket. Although this modification gives the potential to form an extra hydrogen bond to the carboxylate anion of the bacterial cell-wall precursor analogue (N,N)-diacetyl-L-lysyl-D-alanyl-D-alanine, the modified antibiotic does not show enhanced binding to this precursor. This lack of enhanced binding is associated with an unfavourable conformational change (relative to the desired conformation) in the antibiotic.

  我们报告了一种新型糖肽抗生素万古霉素衍生物的合成过程，该衍生物在 N 端进行了修饰。它在抗生素结合袋 N 端位置加入了第四个酰胺 NH。虽然这种修饰有可能与细菌细胞壁前体类似物（N,N)-二乙酰基-L-赖氨酰-D-丙氨酰-D-丙氨酸的羧酸阴离子形成额外的氢键，但修饰后的抗生素与这种前体的结合力并没有增强。这种结合力不强的现象与抗生素的不利构象变化（相对于理想构象）有关。
• Structure−Activity Relationship Studies of a Series of Antiviral and Antibacterial Aglycon Derivatives of the Glycopeptide Antibiotics Vancomycin, Eremomycin, and Dechloroeremomycin
  作者：Svetlana S. Printsevskaya、Svetlana E. Solovieva、Eugenia N. Olsufyeva、Elena P. Mirchink、Elena B. Isakova、Erik De Clercq、Jan Balzarini、Maria N. Preobrazhenskaya

  DOI：10.1021/jm0500774

  日期：2005.6.1

  N-(adamantyl-1)methyl, N-(adamantyl-2), and N-(omega-aminodecyl) amides of vancomycin, eremomycin, and dechloroeremomycin aglycons and their des-(N-Me-D-Leu) derivatives were synthesized and their antibacterial and anti-HIV activities were investigated. Carboxamides with an intact peptide core demonstrated activity against glycopeptide-susceptible and -resistant bacteria (1-32 microM). N-(adamanty

  合成了万古霉素，埃雷霉素和脱氯埃莫霉素糖苷配基的N-（金刚烷基-1）甲基，N-（金刚烷基-2）和N-（ω-氨基癸基）酰胺及其des-（N-Me-D-Leu）衍生物并对其抗菌和抗HIV活性进行了研究。具有完整肽核的羧酰胺表现出对糖肽敏感和耐药细菌（1-32 microM）的活性。埃雷霉素苷元的N-（金刚烷基-1）甲基羧酰胺具有良好的抗逆转录病毒活性（针对HIV-1为1.6 microM）。具有破坏的肽核心[des-（（N-Me-D-Leu）-aglycon酰胺]的化合物对糖肽敏感和耐药细菌均无活性。des-（N-Me-D-Leu）-eremomycin糖苷配基的（金刚烷-1）甲酰胺具有良好的抗逆转录病毒活性（HIV-1的EC50为5.5 microM，HIV-2的EC50为3.5 microM）。埃雷霉素糖苷配基的（金刚烷-1）甲基酰胺及其去-（N-Me-d-Leu）-衍生物是最有前途和选择
• 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.
• BOOTH, PAUL M.;WILLIAMS, DUBLEY H., J. CHEM. SOC. PERKIN TRANS. PT 1,(1989) N2, C. 2335-2339
  作者：BOOTH, PAUL M.、WILLIAMS, DUBLEY H.

  DOI：——

  日期：——
• Reprogramming of the Antibacterial Drug Vancomycin Results in Potent Antiviral Agents Devoid of Antibacterial Activity
  作者：Zsolt Szűcs、Lieve Naesens、Annelies Stevaert、Eszter Ostorházi、Gyula Batta、Pál Herczegh、Anikó Borbás

  DOI：10.3390/ph13070139

  日期：——

  threat to human health and increasing resistance to the existing antiviral drugs necessitates new concepts to expand the therapeutic options. Glycopeptide derivatives have emerged as a promising new class of antiviral agents. To avoid potential antibiotic resistance, these antiviral glycopeptides are preferably devoid of antibiotic activity. We prepared six vancomycin aglycone hexapeptide derivatives with

  甲型和乙型流感病毒是对人类健康的全球威胁，对现有抗病毒药物的耐药性不断增强，因此有必要提出新的概念来扩大治疗选择范围。糖肽衍生物已经成为有前途的新型抗病毒剂。为了避免潜在的抗生素抗性，这些抗病毒糖肽优选地没有抗生素活性。我们制备了六种万古霉素糖苷配基六肽衍生物，目的是获得具有抗流感病毒但无抗菌活性的化合物。其中两个对甲型和乙型流感病毒的复制产生了强大的选择性抑制作用，同时通过去除关键的N端部分成功消除了抗菌活性。此外，这两种分子还可以抵抗其他几种病毒，例如单纯疱疹病毒，