N-(p-nitrobenzyloxycarbonyl)-D-serine methyl ester | 651059-44-8

• 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-(p-nitrobenzyloxycarbonyl)-D-serine methyl ester
• 英文别名: methyl (2R)-3-hydroxy-2-[(4-nitrophenyl)methoxycarbonylamino]propanoate
• CAS: 651059-44-8
• 化学式: C₁₂H₁₄N₂O₇
• 分子量: 298.252
• InChiKey: QAUUPYAUEFCQOB-SNVBAGLBSA-N

物化性质

• 熔点：
  99-100 °C
• 沸点：
  519.6±50.0 °C(Predicted)
• 密度：
  1.395±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.35
• 重原子数：
  21.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  128.0
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N-(p-nitrobenzyloxycarbonyl)-D-serine methyl ester 在 甲醇 、 三氟化硼乙醚 、 potassium trimethylsilonate 、 二异丁基氢化铝 作用下， 以 二氯甲烷 、 氯仿 、 丙酮 、 乙腈 为溶剂， 反应 27.5h， 生成 (6R,7R)-7-tert-Butoxycarbonylamino-3-{(E)-2-[(S)-2,2-dimethyl-3-(4-nitro-benzyloxycarbonyl)-oxazolidin-4-yl]-vinyl}-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 4-methoxy-benzyl ester
  参考文献：
  名称：

  A Mechanism-Based Inhibitor Targeting the dd-Transpeptidase Activity of Bacterial Penicillin-Binding Proteins

  摘要：

  Penicillin-binding proteins (PBPs) are responsible for the final stages of bacterial cell wall assembly. These enzymes are targets of beta-lactam antibiotics. Two of the PBP activities include DD-transpeptidase and DD-carboxypeptidase activities, which carry out the cross-linking of the cell wall and trimming of the peptidoglycan, the major constituent of the cell wall, by an amino acid, respectively. The activity of the latter enzyme moderates the degree of cross-linking of the cell wall, which is carried out by the former. Both these enzymes go through an acyl-enzyme species in the course of their catalytic events. Compound 6, a cephalosporin derivative incorporated with structural features of the peptidoglycan was conceived as an inhibitor specific for DD-transpeptidases. On acylation of the active sites of DD-transpeptidases, the molecule would organize itself in the two active site subsites such that it mimics the two sequestered strands of the bacterial peptidoglycan en route to their cross-linking. Hence, compound 6 is the first inhibitor conceived and designed specifically for inhibition of DD-transpeptidases. The compound was synthesized in 13 steps and was tested with recombinant PBP1b and PBP5 of Escherichia coli, a DD-transpeptidase and a DD-carboxypeptidase, respectively. Compound 6 was a time-dependent and irreversible inhibitor of PBP1b. On the other hand, compound 6 did not interact with PBP5, neither as an inhibitor (reversible or irreversible) nor as a substrate.

  DOI：

  10.1021/ja038445l
• 作为产物：
  描述：

  D-丝氨酸甲酯盐酸盐 、 氯甲酸对硝基苄酯 以 二氯甲烷 为溶剂， 反应 3.0h， 以77%的产率得到N-(p-nitrobenzyloxycarbonyl)-D-serine methyl ester
  参考文献：
  名称：

  A Mechanism-Based Inhibitor Targeting the dd-Transpeptidase Activity of Bacterial Penicillin-Binding Proteins

  摘要：

  Penicillin-binding proteins (PBPs) are responsible for the final stages of bacterial cell wall assembly. These enzymes are targets of beta-lactam antibiotics. Two of the PBP activities include DD-transpeptidase and DD-carboxypeptidase activities, which carry out the cross-linking of the cell wall and trimming of the peptidoglycan, the major constituent of the cell wall, by an amino acid, respectively. The activity of the latter enzyme moderates the degree of cross-linking of the cell wall, which is carried out by the former. Both these enzymes go through an acyl-enzyme species in the course of their catalytic events. Compound 6, a cephalosporin derivative incorporated with structural features of the peptidoglycan was conceived as an inhibitor specific for DD-transpeptidases. On acylation of the active sites of DD-transpeptidases, the molecule would organize itself in the two active site subsites such that it mimics the two sequestered strands of the bacterial peptidoglycan en route to their cross-linking. Hence, compound 6 is the first inhibitor conceived and designed specifically for inhibition of DD-transpeptidases. The compound was synthesized in 13 steps and was tested with recombinant PBP1b and PBP5 of Escherichia coli, a DD-transpeptidase and a DD-carboxypeptidase, respectively. Compound 6 was a time-dependent and irreversible inhibitor of PBP1b. On the other hand, compound 6 did not interact with PBP5, neither as an inhibitor (reversible or irreversible) nor as a substrate.

  DOI：

  10.1021/ja038445l

文献信息

• A Mechanism-Based Inhibitor Targeting the <scp>dd</scp>-Transpeptidase Activity of Bacterial Penicillin-Binding Proteins
  作者：Mijoon Lee、Dusan Hesek、Maxim Suvorov、Wenlin Lee、Sergei Vakulenko、Shahriar Mobashery

  DOI：10.1021/ja038445l

  日期：2003.12.1

  Penicillin-binding proteins (PBPs) are responsible for the final stages of bacterial cell wall assembly. These enzymes are targets of beta-lactam antibiotics. Two of the PBP activities include DD-transpeptidase and DD-carboxypeptidase activities, which carry out the cross-linking of the cell wall and trimming of the peptidoglycan, the major constituent of the cell wall, by an amino acid, respectively. The activity of the latter enzyme moderates the degree of cross-linking of the cell wall, which is carried out by the former. Both these enzymes go through an acyl-enzyme species in the course of their catalytic events. Compound 6, a cephalosporin derivative incorporated with structural features of the peptidoglycan was conceived as an inhibitor specific for DD-transpeptidases. On acylation of the active sites of DD-transpeptidases, the molecule would organize itself in the two active site subsites such that it mimics the two sequestered strands of the bacterial peptidoglycan en route to their cross-linking. Hence, compound 6 is the first inhibitor conceived and designed specifically for inhibition of DD-transpeptidases. The compound was synthesized in 13 steps and was tested with recombinant PBP1b and PBP5 of Escherichia coli, a DD-transpeptidase and a DD-carboxypeptidase, respectively. Compound 6 was a time-dependent and irreversible inhibitor of PBP1b. On the other hand, compound 6 did not interact with PBP5, neither as an inhibitor (reversible or irreversible) nor as a substrate.