Vancomycin ketone | 249739-76-2

• 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: Vancomycin ketone
• 英文别名: (1S,2R,18R,19R,22S,25R,28R,40S)-48-[(2S,3R,4S,5S,6R)-3-[(2S,4S,5S,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)-5,15-dichloro-2,18,32,35,37-pentahydroxy-19-[(4-methyl-2-oxopentanoyl)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-3,5,8(48),9,11,14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylic acid
• CAS: 249739-76-2
• 化学式: C₆₅H₇₀Cl₂N₈O₂₅
• 分子量: 1434.22
• InChiKey: QUMBSOVNROUGJD-AXKZAMRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  100
• 可旋转键数：
  12
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  536
• 氢给体数：
  18
• 氢受体数：
  26

反应信息

• 作为反应物：
  描述：

  Vancomycin ketone 在 吡啶 、 盐酸羟胺 作用下， 以 甲醇 为溶剂， 反应 20.0h， 以67%的产率得到(Z)-Vancomycin oxime
  参考文献：
  名称：

  The synthesis and binding of N-terminal derivatives of vancomycin to a bacterial cell wall analogue

  摘要：

  We report the synthesis of novel derivatives of the glycopeptide antibiotic vancomycin, modified at the N-terminus. Binding constants were measured for the association of these derivatives with the tripeptide analogue N,N-diacetyl-L-lysyl-D-alanyl-D-alanine. Replacement of the sp3 centre of the leucine residue of vancomycin with an sp2 centre resulted in weaker binding in all cases. These findings contrast with the relatively strong binding of some of the analogous derivatives previously obtained from ristocetin A. The reduction in the binding affinities of the vancomycin derivatives is attributed to a conformational change in the antibiotic which is not possible in the analogous derivatives of the aglycone of ristocetin.

  DOI：

  10.1039/a903971f
• 作为产物：
  描述：

  去甲万古霉素 在 acetate buffer 、 copper(II) sulfate 、 乙醛酸 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以81%的产率得到Vancomycin ketone
  参考文献：
  名称：

  The synthesis and binding of N-terminal derivatives of vancomycin to a bacterial cell wall analogue

  摘要：

  We report the synthesis of novel derivatives of the glycopeptide antibiotic vancomycin, modified at the N-terminus. Binding constants were measured for the association of these derivatives with the tripeptide analogue N,N-diacetyl-L-lysyl-D-alanyl-D-alanine. Replacement of the sp3 centre of the leucine residue of vancomycin with an sp2 centre resulted in weaker binding in all cases. These findings contrast with the relatively strong binding of some of the analogous derivatives previously obtained from ristocetin A. The reduction in the binding affinities of the vancomycin derivatives is attributed to a conformational change in the antibiotic which is not possible in the analogous derivatives of the aglycone of ristocetin.

  DOI：

  10.1039/a903971f

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。