Cbz-Lys(Cbz)-DAla-OH | 122242-30-2

• 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: Cbz-Lys(Cbz)-DAla-OH
• 英文别名: N-(N²,N⁶-bis-benzyloxycarbonyl-L-lysyl)-D-alanine；N-(N²,N⁶-Bis-benzyloxycarbonyl-L-lysyl)-D-alanin；α-Z-ε-Z-Lys-D-Ala-OH
• CAS: 122242-30-2；122242-29-9
• 化学式: C₂₅H₃₁N₃O₇
• 分子量: 485.537
• InChiKey: WFHCOXRKGXHXNZ-NQIIRXRSSA-N

物化性质

• 沸点：
  778.0±60.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  35.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  143.06
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  Cbz-Lys(Cbz)-DAla-OH 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 生成 Lys-D-Ala-OH
  参考文献：
  名称：

  Goldschmidt,S.; Rosculet,G., Chemische Berichte, 1960, vol. 93, p. 2387 - 2394

  摘要：

  DOI：
• 作为产物：
  描述：

  N,N’-双苄氧羰基-L-赖氨酸 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 19.0h， 生成 Cbz-Lys(Cbz)-DAla-OH
  参考文献：
  名称：

  Structure Diversification of Vancomycin through Peptide-Catalyzed, Site-Selective Lipidation: A Catalysis-Based Approach To Combat Glycopeptide-Resistant Pathogens

  摘要：

  The emergence of antibiotic-resistant infections highlights the need for novel antibiotic leads, perhaps with a broader spectrum of activity. Herein, we disclose a semisynthetic, catalytic approach for structure diversification of vancomycin. We have identified three unique peptide catalysts that exhibit site-selectivity for the lipidation of the aliphatic hydroxyls on vancomycin, generating three new derivatives 9a, 9b, and 9c. Incorporation of lipid chains into the vancomycin scaffold provides promising improvement of its bioactivity against vancomycin-resistant enterococci (Van A and Van B phenotypes of VRE). The MICs for 9a, 9b, and 9c against MRSA and VRE (Van B phenotype) range from 0.12 to 0.25 mu g/mL. We have also performed a structure-activity relationship (SAR) study to investigate the effect of lipid chain length at the newly accessible G(4)-OH derivatization site.

  DOI：

  10.1021/jm501872s

文献信息

• Antibiotic Activities and Affinities for Bacterial Cell Wall Analogue of N-Demethylvancomycin and Its Derivatives.
  作者：HUSHENG YAN、DONGFENG QI、XIAOHUI CHENG、ZHENGJI SONG、WENLAN LI、BINGLIN HE

  DOI：10.7164/antibiotics.51.750

  日期：——

  constants of the complexes of N-demethylvancomycin and its analogues with di-N-Ac-L-Lys-D-Ala-D-Ala and the antibiotic activity against Staphylococcus aureus of the glycopeptides were determined. Results showed that N-demethylvancomycin has higher affinity for bacterial cell wall analogue di-N-Ac-L-Lys-D-Ala-D-Ala and more potent antibiotic activity against Staphylococcus aureus than vancomycin. Both

  N-去甲基万古霉素已在中国临床使用，是万古霉素类（糖肽）抗生素的一种。它与万古霉素的不同之处仅在于万古霉素N末端残基的氨基上的甲基已被H取代。通过N-去甲基万古霉素的还原烷基化反应，我们合成了N-烷基和N，N'-二烷基N-去甲基万古霉素与万古霉素的结构密切相关。测定了N-去甲基万古霉素及其类似物与di-N-Ac-L-Lys-D-Ala-D-Ala的配合物的缔合常数以及糖肽对金黄色葡萄球菌的抗生素活性。结果表明，N-去甲基万古霉素对细菌细胞壁类似物di-N-Ac-L-Lys-D-Ala-D-Ala具有比万古霉素更高的对金黄色葡萄球菌的抗菌活性。N-去甲基万古霉素的N-烷基化和N，N'-二烷基化均降低了亲和力和抗生素活性。烷基越长，糖肽的抗菌活性越低，亲和力越低。N-去甲基万古霉素及其类似物对金黄色葡萄球菌的抗生素活性大致平行​​于它们对di-N-Ac-L-Lys-D-Ala-D-Ala的亲和力。
• Optical Rotation of Peptides. III. Lysine Dipeptides¹
  作者：Bernard F. Erlanger、Erwin Brand

  DOI：10.1021/ja01152a519

  日期：1951.8
• Catalytic Site-Selective Thiocarbonylations and Deoxygenations of Vancomycin Reveal Hydroxyl-Dependent Conformational Effects
  作者：Brandon S. Fowler、Kai M. Laemmerhold、Scott J. Miller

  DOI：10.1021/ja302692j

  日期：2012.6.13

  We have examined peptide-based catalysts for the site-selective thiocarbonylation of a protected form of vancomycin. Several catalysts were identified that either enhanced or altered the inherent selectivity profile exhibited by the substrate. Two catalysts, one identified through screening and another through rational design, were demonstrated to be effective on 0.50-g scale. Deoxygenations led ultimately to two new deoxy-vancomycin derivatives, and surprising conformational consequences of deoxygenation were revealed for one of the new compounds. These effects were mirrored in the biological activities of the new analogues and support a structural role for certain hydroxyls in the native structure.