N-carboxybenzoxy-L-alanyl-D,L-2-hydroxyglycine benzyl ester | 89625-83-2

• 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: N-carboxybenzoxy-L-alanyl-D,L-2-hydroxyglycine benzyl ester
• 英文别名: N-carbobenzyloxy-L-alanyl-D,L-2-hydroxyglycine benzyl ester；benzyl 2-hydroxy-2-[[(2S)-2-(phenylmethoxycarbonylamino)propanoyl]amino]acetate
• CAS: 89625-83-2
• 化学式: C₂₀H₂₂N₂O₆
• 分子量: 386.404
• InChiKey: WAFCJRKFFXWVDC-PIVQAISJSA-N

物化性质

• 沸点：
  621.0±55.0 °C(Predicted)
• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-carboxybenzoxy-L-alanyl-D,L-2-hydroxyglycine benzyl ester 在 吡啶 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 N-carboxybenzoxy-L-alanyl-2-(5-fluorouracil-1-yl)-D,L-glycine benzyl ester
  参考文献：
  名称：

  A novel peptide delivery system involving peptidase activated prodrugs as antimicrobial agents. Synthesis and biological activity of peptidyl derivatives of 5-fluorouracil

  摘要：

  As an approach to the development of antimicrobial agents, a novel peptide carrier system was designed, based on the chemical instability of alpha-substituted glycine analogues, with the explicit intent of actively transporting therapeutically useful compounds into microbial cells. Peptides containing 5-fluorouracil (5-FU) linked to the peptide backbone were selected to test the feasibility of this new delivery system. These peptide conjugates were designed such that they would be substrates for both the microbial peptide permeases and peptidases. After entry into cells, enzymatic hydrolysis of the peptide generates an unstable alpha-(5-FU)-glycine that spontaneously decomposes to release 5-FU. The 5-FU-peptide conjugates were tested for antifungal (Candida albicans) and antibacterial (Escherichia coli) activity and were found to have antimicrobial activities comparable to free 5-FU. Noninhibitory peptides antagonized the antimicrobial activities of the 5-FU-peptide conjugates but not of free 5-FU, a result consistent with peptide transport mediated entry of the peptide conjugates into cells. Further support for this conclusion was provided by the finding that biological activities were dependent upon peptide stereochemistry.

  DOI：

  10.1021/jm00377a012
• 作为产物：
  描述：

  苄基2-氧代乙酸酯 、 Z-L-丙氨酰胺 在 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 168.0h， 以70%的产率得到N-carboxybenzoxy-L-alanyl-D,L-2-hydroxyglycine benzyl ester
  参考文献：
  名称：

  具有独特的氨基，半胱氨酸和半硫代氨基官能团的5'-核苷单磷酸酯衍生物的合成：一类新的5'-肽基核苷酸

  摘要：

  已开发出许多合成上有用的转化形式，以产生新的5'-肽基核苷单磷酸类似物，这些类似物结合了敏感的磷酸氨基，半胱氨酸或半硫代氨基缩醛官能团。所采用的策略需要二肽之间的偶联，从而封闭了一个反应性的Cα-官能化的甘氨酸残基和磷酸或硫代磷酸酯基团。这些进展为制备α-磷酸化假肽以及核苷单磷酸酯模拟物带来了潜在的强大而通用的方法学。所得的缀合物对于从药物开发到合成生物学的各种重要应用都是令人感兴趣的，它们是用于异源生物信息系统酶促合成的前核苷酸或人工结构单元。

  DOI：

  10.1002/chem.201600721

文献信息

• Oligopeptide prodrugs
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0094815B1

  公开（公告）日：1989-01-11
• Syntheses of 5′-Nucleoside Monophosphate Derivatives with Unique Aminal, Hemiaminal, and Hemithioaminal Functionalities: A New Class of 5′-Peptidyl Nucleotides
  作者：Swarup De、Elisabetta Groaz、Lia Margamuljana、Piet Herdewijn

  DOI：10.1002/chem.201600721

  日期：2016.6.6

  A number of synthetically useful transformations have been developed to generate novel 5′‐peptidyl nucleoside monophosphate analogues that incorporate sensitive phosphoaminal, ‐hemiaminal or ‐hemithioaminal functionalities. The strategies adopted entailed the coupling between dipeptides, which enclose a reactive Cα‐functionalized glycine residue and phosphate or phosphorothioate moieties. These developments

  已开发出许多合成上有用的转化形式，以产生新的5'-肽基核苷单磷酸类似物，这些类似物结合了敏感的磷酸氨基，半胱氨酸或半硫代氨基缩醛官能团。所采用的策略需要二肽之间的偶联，从而封闭了一个反应性的Cα-官能化的甘氨酸残基和磷酸或硫代磷酸酯基团。这些进展为制备α-磷酸化假肽以及核苷单磷酸酯模拟物带来了潜在的强大而通用的方法学。所得的缀合物对于从药物开发到合成生物学的各种重要应用都是令人感兴趣的，它们是用于异源生物信息系统酶促合成的前核苷酸或人工结构单元。
• A novel peptide delivery system involving peptidase activated prodrugs as antimicrobial agents. Synthesis and biological activity of peptidyl derivatives of 5-fluorouracil
  作者：William D. Kingsbury、Jeffrey C. Boehm、Rajanikant J. Mehta、Sarah F. Grappel、Charles Gilvarg

  DOI：10.1021/jm00377a012

  日期：1984.11

  As an approach to the development of antimicrobial agents, a novel peptide carrier system was designed, based on the chemical instability of alpha-substituted glycine analogues, with the explicit intent of actively transporting therapeutically useful compounds into microbial cells. Peptides containing 5-fluorouracil (5-FU) linked to the peptide backbone were selected to test the feasibility of this new delivery system. These peptide conjugates were designed such that they would be substrates for both the microbial peptide permeases and peptidases. After entry into cells, enzymatic hydrolysis of the peptide generates an unstable alpha-(5-FU)-glycine that spontaneously decomposes to release 5-FU. The 5-FU-peptide conjugates were tested for antifungal (Candida albicans) and antibacterial (Escherichia coli) activity and were found to have antimicrobial activities comparable to free 5-FU. Noninhibitory peptides antagonized the antimicrobial activities of the 5-FU-peptide conjugates but not of free 5-FU, a result consistent with peptide transport mediated entry of the peptide conjugates into cells. Further support for this conclusion was provided by the finding that biological activities were dependent upon peptide stereochemistry.