N-acetyl-D-aspartic acid β-benzyl ester | 163929-78-0

• 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-acetyl-D-aspartic acid β-benzyl ester
• 英文别名: β-benzyl-N-acetyl-D-asparagine；4-(Phenylmethyl) hydrogen N-acetyl-D-aspartate；(2R)-2-acetamido-4-oxo-4-phenylmethoxybutanoic acid
• CAS: 163929-78-0
• 化学式: C₁₃H₁₅NO₅
• 分子量: 265.266
• InChiKey: HGRQBCVXVCWXLS-LLVKDONJSA-N

物化性质

• 沸点：
  538.8±50.0 °C(Predicted)
• 密度：
  1.267±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-acetyl-D-aspartic acid β-benzyl ester 在 palladium on activated charcoal 、 三乙胺 4-二甲氨基吡啶 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、206.84 kPa 条件下， 生成 (R)-3-Acetylamino-N-hydroxy-succinamic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of hydroxamate-Based inhibitors of glutamate carboxypeptidase II

  摘要：

  A series of hydroxamic acids has been prepared as potential inhibitors of glutamate carboxypeptidase II (GCP II). Compounds based on a Pl' residue (primed-side inhibitors) were more potent than those based on a Pl group (unprimed-side inhibitors). Inhibitory potency of the primed-side GCP II inhibitors was found to be dependent on the number of methylene units between the hydroxamate group and pentanedioic acid. Succinyl hydroxamic acid derivative, 2-(hydroxycarbamoylmethyl)pentanedioic acid, is the most potent GCP II inhibitor with an IC50 value of 220 nM The comparison of the results to those of other classes of GCP II inhibitors as well as hydroxamate-based MNIP inhibitors provides further insight into the structure-activity relationships of GCP II inhibition. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00407-4
• 作为产物：
  描述：

  β-Benzyl-D-aspartat 、 乙酸酐 在 sodium acetate 作用下， 以 水 为溶剂， 反应 0.05h， 生成 N-acetyl-D-aspartic acid β-benzyl ester
  参考文献：
  名称：

  Antibody-Catalyzed Rearrangement of a Peptide Bond: Mechanistic and Kinetic Investigations

  摘要：

  Catalysis of the deamidation of asparagine residues may provide a powerful method for the deactivation of proteins. Catalytic antibodies (Gibbs et al. Science 1992, 258, 803) have been induced that catalyze the deamidation of a model dipeptide through an intermediate succinimide. Investigations of the mechanistic characteristics of two such antibodies, RG2-23C7 and RG2-2E4, revealed their ability to accelerate the hydrolysis of either the R- or S-enantiomers of the succinimide by factors of 10-500-fold to yield differing ratios of the aspartate and isoaspartate products. The mixed product ratios imply that two tetrahedral binding sites of unequal effectiveness were induced in response to the tetrahedral mimics (a phosphinate or secondary hydroxyl) within the hapten structure. The antibody RG2-2E4 also catalyzes the deamidation of either the D- or L-asparagine within the dipeptide through the intermediate cyclic imide, resulting in a multistep reaction sequence featuring a series of tetrahedral transition states. pH-rate profiles do not implicate functional groups within the antibodies' combining sites for either the deamidation or hydrolytic reactions. The strategy of bifunctional or higher order transition state mimics should provide a route to developing catalytic antibodies for reactions requiring multistep processing.

  DOI：

  10.1021/ja00122a001

文献信息

• Antibody-Catalyzed Rearrangement of a Peptide Bond: Mechanistic and Kinetic Investigations
  作者：Louis J. Liotta、Richard A. Gibbs、Scott D. Taylor、Patricia A. Benkovic、Stephen J. Benkovic

  DOI：10.1021/ja00122a001

  日期：1995.5

  Catalysis of the deamidation of asparagine residues may provide a powerful method for the deactivation of proteins. Catalytic antibodies (Gibbs et al. Science 1992, 258, 803) have been induced that catalyze the deamidation of a model dipeptide through an intermediate succinimide. Investigations of the mechanistic characteristics of two such antibodies, RG2-23C7 and RG2-2E4, revealed their ability to accelerate the hydrolysis of either the R- or S-enantiomers of the succinimide by factors of 10-500-fold to yield differing ratios of the aspartate and isoaspartate products. The mixed product ratios imply that two tetrahedral binding sites of unequal effectiveness were induced in response to the tetrahedral mimics (a phosphinate or secondary hydroxyl) within the hapten structure. The antibody RG2-2E4 also catalyzes the deamidation of either the D- or L-asparagine within the dipeptide through the intermediate cyclic imide, resulting in a multistep reaction sequence featuring a series of tetrahedral transition states. pH-rate profiles do not implicate functional groups within the antibodies' combining sites for either the deamidation or hydrolytic reactions. The strategy of bifunctional or higher order transition state mimics should provide a route to developing catalytic antibodies for reactions requiring multistep processing.
• Synthesis and biological evaluation of hydroxamate-Based inhibitors of glutamate carboxypeptidase II
  作者：Doris Stoermer、Qun Liu、Monicia R Hall、Juliet M Flanary、Ajit G Thomas、Camilo Rojas、Barbara S Slusher、Takashi Tsukamoto

  DOI：10.1016/s0960-894x(03)00407-4

  日期：2003.7

  A series of hydroxamic acids has been prepared as potential inhibitors of glutamate carboxypeptidase II (GCP II). Compounds based on a Pl' residue (primed-side inhibitors) were more potent than those based on a Pl group (unprimed-side inhibitors). Inhibitory potency of the primed-side GCP II inhibitors was found to be dependent on the number of methylene units between the hydroxamate group and pentanedioic acid. Succinyl hydroxamic acid derivative, 2-(hydroxycarbamoylmethyl)pentanedioic acid, is the most potent GCP II inhibitor with an IC50 value of 220 nM The comparison of the results to those of other classes of GCP II inhibitors as well as hydroxamate-based MNIP inhibitors provides further insight into the structure-activity relationships of GCP II inhibition. (C) 2003 Elsevier Science Ltd. All rights reserved.