伊瑞霉素 | 110865-90-2

• 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
• 中文名称: 伊瑞霉素
• 英文名称: Eremomycin
• 英文别名: (1S,2R,18R,19R,22S,25R,28R,40S)-2-[(2R,4S,5R,6S)-4-amino-5-hydroxy-4,6-dimethyloxan-2-yl]oxy-48-[(2S,3R,4S,5S,6R)-3-[(2R,4S,5R,6S)-4-amino-5-hydroxy-4,6-dimethyloxan-2-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-(2-amino-2-oxoethyl)-15-chloro-18,32,35,37-tetrahydroxy-19-[[(2R)-4-methyl-2-(methylamino)pentanoyl]amino]-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(50),4,6(49),8(48),9,11,14,16,29(45),30,32,34(39),35,37,46-pentadecaene-40-carboxylic acid
• CAS: 110865-90-2
• 化学式: C₇₃H₈₉ClN₁₀O₂₆
• 分子量: 1558.01
• InChiKey: UECIPBUIMXSXEI-BNSVOVDNSA-N

物化性质

• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.4
• 重原子数：
  110
• 可旋转键数：
  15
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  575
• 氢给体数：
  20
• 氢受体数：
  29

反应信息

• 作为反应物：
  描述：

  伊瑞霉素 在 barium dihydroxide 、 水 作用下， 反应 4.0h， 以33%的产率得到carboxyeremomycin
  参考文献：
  名称：

  Olsufyeva, Eugenia N.; Berdnikova, Tatiana F.; Miroshnikova, Olga V., Journal of Antibiotics, 1999, vol. 52, # 3, p. 319 - 324

  摘要：

  DOI：
• 作为产物：
  描述：

  carboxyeremomycin 在 氯化铵 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 0.42h， 以37%的产率得到carboxyeremomycin AA7-amide
  参考文献：
  名称：

  New derivatives of eremomycin containing 15N or F atoms for NMR study

  摘要：

  New semisynthetic derivatives of eremomycin containing N-15 or F atoms were obtained for studying the antibiotic-target interaction in intact cells of Gram-positive bacteria by REDOR NMR method. Interaction of the terminal carboxyl group of amino acid 7 (AA7) of eremomycin with amines in the presence of PyBOP and TBTU reagents resulted in the corresponding [N-15]-amide, p-fluorobenzylamide, p-fluorophenylpiperazide, and 6-N-(p-fluorobenzyl)aminohexylamide. A selective method of [N-15]-amidation of carboxyl group of amino acid 3 (AA3) of carboxyeremomycin was developed, and the amide of eremomycin containing [N-15] in AA3 amide group near the antibiotic binding pocket was obtained. Carboxyeremomycin bisamides substituted at AA3 and AA7 and containing two atoms of [N-15] or F were obtained from carboxyeremomycin and [N-15]NH4Cl or the corresponding p-fluorobenzylamine hydrochloride in the presence of PyBOP at pH similar to 8. The Edman degradation of eremomycin p-fluorobenzylamide gave de-(D-MeLeu)-eremomycin p-fluorobenzylamide, a hexapeptide derivative incapable of the antibiotic binding with -D-Ala-D-Ala fragment of growing cell wall peptidoglycan. Among the compounds studied, carboxyeremomycin bis-p-fluorobenzylamide showed the best activity against both the glycopeptides-sensitive and glycopeptides-resistant strains of staphylococci and enterococci.

  DOI：

  10.1134/s1068162008060162

文献信息

• Reductive Alkylation of Glycopeptide Antibiotics: Synthesis and Antibacterial Activity.
  作者：ROBIN D. G. COOPER、NANCY J. SNYDER、MARK J. ZWEIFEL、MICHAEL A. STASZAK、STEPHEN C. WILKIE、THALIA I. NICAS、DEBORAH L. MULLEN、THOMAS F. BUTLER、MICHAEL J. RODRIGUEZ、BRET E. HUFF、RICHARD C. THOMPSON

  DOI：10.7164/antibiotics.49.575

  日期：——

  Reductive alkylation of the A82846 family of glycopeptide antibiotics has the potential of producing seven products. N-Alkylation of the disaccharide amino function can be accomplished selectively, and offers the greatest increase in antibacterial activity. Products resulting from N-alkylation of LY264826 (A82846B) provide the most potent derivatives as compared to other members of this class of antibiotics. Two of these derivatives, LY307599 and LY333328 are approximately 500 times more active than vancomycin against vancomycin-resistant enterococci.

  A82846类糖肽抗生素的还原烷基化有潜力产生七种产物。二糖氨基功能的N-烷基化可以选择性地完成，并提供最大的抗菌活性提升。与这一类抗生素的其他成员相比，由N-烷基化的LY264826（A82846B）产生的产物提供了最强效的衍生物。这些衍生物中的两个，LY307599和LY333328，相比于万古霉素对万古霉素耐药肠球菌的活性约高出500倍。
• Antiretroviral Activity of Semisynthetic Derivatives of Glycopeptide Antibiotics
  作者：Jan Balzarini、Christophe Pannecouque、Erik De Clercq、Andrey Y. Pavlov、Svetlana S. Printsevskaya、Olga V. Miroshnikova、Marina I. Reznikova、Maria N. Preobrazhenskaya

  DOI：10.1021/jm0300882

  日期：2003.6.1

  natural antibacterial glycopeptide antibiotics such as vancomycin, eremomycin, ristocetin A, teicoplanin A(2)-2, DA-40926, their aglycons, and also the products of their partial degradation with a destroyed or modified peptide core show marked anti-retroviral activity in cell culture. In particular, aglycon antibiotic derivatives containing various substituents of a preferably hydrophobic nature displayed

  多种天然抗菌糖肽抗生素的半合成衍生物，例如万古霉素，埃雷霉素，瑞斯托菌素A，替考拉宁A（2）-2，DA-40926，它们的糖苷配基，以及具有被破坏或修饰的肽核的部分降解产物在细胞培养中具有明显的抗逆转录病毒活性。尤其是，含有优选具有疏水性的各种取代基的糖苷配基抗生素衍生物在较低的微摩尔浓度下（50％抑制浓度）显示出对人类免疫缺陷病毒1型（HIV-1），HIV-2和莫洛尼鼠肉瘤病毒的活性（1-浓度范围为5 microM），而在250 microM或更高的浓度下不会对人淋巴细胞产生细胞抑制作用。抗生素糖苷配基衍生物的抗HIV作用方式可归因于病毒进入过程的抑制。
• Synthesis and Mode of Action of Hydrophobic Derivatives of the Glycopeptide Antibiotic Eremomycin and Des-(<i>N</i>-methyl-<scp>d</scp>-leucyl)eremomycin against Glycopeptide-Sensitive and -Resistant Bacteria
  作者：Svetlana S. Printsevskaya、Andrey Y. Pavlov、Evgenia N. Olsufyeva、Elena P. Mirchink、Elena B. Isakova、Marina I. Reznikova、Robert C. Goldman、Arthur A. Branstrom、Eugene R. Baizman、Clifford B. Longley、Ferenc Sztaricskai、Gyula Batta、Maria N. Preobrazhenskaya

  DOI：10.1021/jm010460i

  日期：2002.3.1

  was obtained by Edman degradation of eremomycin. Derivatives with a hydrophobic substituent at the exterior of the molecule were then synthesized, and their antibacterial activities were compared with similar derivatives of eremomycin. Comparison of derivatives of eremomycin containing the n-decyl or p-(p-chlorophenyl)benzyl substituent in the eremosamine moiety (N') and n-decyl or p-(p-chlorophenyl)benzylamides

  Des-（N-甲基-D-亮氨酰）eremomycin是通过Edman降解ememomycin获得的。然后合成在分子外部具有疏水取代基的衍生物，并将其抗菌活性与埃雷霉素的类似衍生物进行比较。比较埃雷莫胺部分（N'）中含有正癸基或对-（对氯苯基）苄基的埃雷霉素衍生物和正癸基或对-（对氯苯基）苄基酰胺与具有受损肽的埃雷霉素类似衍生物的比较核心（有缺陷的结合口袋）表明，这两种类型的化合物对肠球菌（GRE）的糖肽耐药菌株几乎具有相同的活性，而埃雷霉素衍生物对葡萄球菌的活性更高。埃雷霉素的疏水7d-烷基氨基甲基化衍生物（9，10）表现出相似的抗菌性能。由于糖肽类抗生素的基本作用方式涉及与终止于-D-Ala-D-Ala的细胞壁中间体的结合，并且六肽衍生物中的这种相互作用被严重降低（缺乏关键的N-甲基-D-亮氨酸），我们建议这些疏水性衍生物可以在不存在二肽结合的情况下抑制肽聚糖的合成。使用Ac-D-Ala