methyl 2-acetamido-4,6-O-benzylidene-3-O-((R)-1'-carboxyethyl)-2-deoxy-β-D-glucopyranoside | 129172-14-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃二恶英
• 英文名称: methyl 2-acetamido-4,6-O-benzylidene-3-O-((R)-1'-carboxyethyl)-2-deoxy-β-D-glucopyranoside
• 英文别名: (2R)-2-[[(2R,4aR,6R,7R,8R,8aS)-7-acetamido-6-methoxy-2-phenyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy]propanoic acid
• CAS: 129172-14-1
• 化学式: C₁₉H₂₅NO₈
• 分子量: 395.409
• InChiKey: PDAYKQHANSZCPY-SNIXWPOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 2-acetamido-4,6-O-benzylidene-3-O-((R)-1'-carboxyethyl)-2-deoxy-β-D-glucopyranoside 在 吡啶 、 三乙基硅烷 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 (2R)-2-[(2R,3S,4R,5R,6R)-5-acetamido-2-(acetyloxymethyl)-6-methoxy-3-phenylmethoxyoxan-4-yl]oxypropanoic acid
  参考文献：
  名称：

  淋病奈瑟氏球菌肽聚糖修饰酶O-乙酰肽肽聚糖酯酶（Ape1）的水溶性底物

  摘要：

  肽聚糖是细菌细胞壁的组成部分，对于维持细胞的形状和刚性至关重要。这样，由N-乙酰基葡糖胺（GlcNAc）和N-乙酰基尿酸（MurNAc）的交替单元组成的其聚合结构也是宿主防御酶如溶菌酶的作用的靶标。许多细菌已经开发出通过添加糖苷配基部分来掩盖其细胞壁免受这些环境危害的方法，所述糖苷配基部分阻止识别或在空间上阻碍外源酶的降解作用，否则会损害细胞。肽聚糖乙酰基转移酶（Pat's）和O-乙酰基肽聚糖酯酶（Ape's）是负责将乙酸盐控制添加到肽聚糖中MurNAc残基的C-6羟基上并从中去除的酶。对淋病奈瑟氏菌中发现的一种O-乙酰基肽聚糖酯酶Ape1的研究表明，该酶对于细菌生存力是必不可少的，因此为抗菌设计提出了一个有吸引力的目标。由于Ape1的天然底物是不溶性聚合物，因此以前对Ape1的研究受到了阻碍。在本文中，我们概述了水溶性二糖和单糖底物类似物1和2的设计，合成和测试。既1和2作为与APE1的基板k

  DOI：

  10.1021/jo102329c
• 作为产物：
  描述：

  甲基 2-乙酰氨基-3,4,6-O-三乙酰基-2-脱氧-beta-D-吡喃葡萄糖苷 在 4 A molecular sieve 、 sodium methylate 、 sodium hydride 、 对甲苯磺酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.5h， 生成 methyl 2-acetamido-4,6-O-benzylidene-3-O-((R)-1'-carboxyethyl)-2-deoxy-β-D-glucopyranoside
  参考文献：
  名称：

  Synthetic Peptidoglycan Substrates for Penicillin-Binding Protein 5 of Gram-Negative Bacteria

  摘要：

  The major constituent of the bacterial cell wall, peptidoglycan, is comprised of repeating units of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) with an appended peptide. Penicillin-binding proteins (PBPs) are involved in the final stages of bacterial cell wall assembly. Two activities for PBPs are the cross-linking of the cell wall, carried out by DD-transpeptidases, and the DD-peptidase activity, that removes the terminal D-Ala residue from peptidoglycan. The DD-peptidase activity moderates the extent of the cell wall cross-linking. There exists a balance between the two activities that is critical for the well-being of bacterial cells. We have cloned and purified PBP5 of Escherichia coli. The membrane anchor of this protein was removed, and the enzyme was obtained as a soluble protein. Two fragments of the polymeric cell wall of Gram-negative bacteria (compounds 5 and 6) were synthesized. These molecules served as substrates for PBP5. The products of the reactions of PBP5 and compounds 5 and 6 were isolated and were shown to be D-Ala and the fragments of the substrates minus the terminal D-Ala. The kinetic parameters for these enzymic reactions were evaluated. PBP5 would appear to have the potential for turnover of as many as 1.4 million peptidoglycan strands within a single doubling time (i.e., generation) of E. coli.

  DOI：

  10.1021/jo035397e

文献信息

• Activation for Catalysis of Penicillin-Binding Protein 2a from Methicillin-Resistant <i>Staphylococcus </i><i>a</i><i>ureus</i> by Bacterial Cell Wall
  作者：Cosimo Fuda、Dusan Hesek、Mijoon Lee、Ken-ichiro Morio、Thomas Nowak、Shahriar Mobashery

  DOI：10.1021/ja0434376

  日期：2005.2.1

  Methicillin-resistant Staphylococcus aureus (MRSA) has acquired a unique penicillin-binding protein (PBP), PBP 2a, which has rendered the organism resistant to the action of all available beta-lactam antibiotics. The X-ray structure of PBP 2a shows the active site in a closed conformation, consistent with resistance to inhibition by beta-lactam antibiotics. However, it is known that PBP 2a avidly cross-links the S. aureus cell wall, which is its physiological function. It is shown herein that synthetic fragments of the bacterial cell wall bind in a saturable manner to PBP 2a and cause a conformational change in the protein that makes the active site more accessible to binding to a beta-lactam antibiotic. These observations and measurements point to a novel strategy by nature to keep the active site of PBP 2a sheltered from the inhibitory activity of the antibiotics, yet it becomes available to the polymeric cell wall by a requisite conformational change for the critical cell wall cross-linking reaction.
• Synthetic Peptidoglycan Substrates for Penicillin-Binding Protein 5 of Gram-Negative Bacteria
  作者：Dusan Hesek、Maxim Suvorov、Ken-ichiro Morio、Mijoon Lee、Stephen Brown、Sergei B. Vakulenko、Shahriar Mobashery

  DOI：10.1021/jo035397e

  日期：2004.2.1

  The major constituent of the bacterial cell wall, peptidoglycan, is comprised of repeating units of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) with an appended peptide. Penicillin-binding proteins (PBPs) are involved in the final stages of bacterial cell wall assembly. Two activities for PBPs are the cross-linking of the cell wall, carried out by DD-transpeptidases, and the DD-peptidase activity, that removes the terminal D-Ala residue from peptidoglycan. The DD-peptidase activity moderates the extent of the cell wall cross-linking. There exists a balance between the two activities that is critical for the well-being of bacterial cells. We have cloned and purified PBP5 of Escherichia coli. The membrane anchor of this protein was removed, and the enzyme was obtained as a soluble protein. Two fragments of the polymeric cell wall of Gram-negative bacteria (compounds 5 and 6) were synthesized. These molecules served as substrates for PBP5. The products of the reactions of PBP5 and compounds 5 and 6 were isolated and were shown to be D-Ala and the fragments of the substrates minus the terminal D-Ala. The kinetic parameters for these enzymic reactions were evaluated. PBP5 would appear to have the potential for turnover of as many as 1.4 million peptidoglycan strands within a single doubling time (i.e., generation) of E. coli.
• Water-Soluble Substrates of the Peptidoglycan-Modifying Enzyme <i>O-</i>Acetylpeptidoglycan Esterase (Ape1) from <i>Neisseria gonorrheae</i>
  作者：Timin Hadi、John M. Pfeffer、Anthony J. Clarke、Martin E. Tanner

  DOI：10.1021/jo102329c

  日期：2011.2.18

  of the water-soluble di- and monosaccharide substrate analogues 1 and 2. Both 1 and 2 serve as substrates of Ape1 with kcat/KM values of (5.1 ± 1.7) × 103 M−1 s−1 and (3.1 ± 0.8) × 103 M−1 s−1, respectively. It was determined that the substitution of the GlcNAc residue in compound 1 with an O-benzyl group in compound 2 did not significantly decrease the enzyme’s affinity for the monosaccharide. These

  肽聚糖是细菌细胞壁的组成部分，对于维持细胞的形状和刚性至关重要。这样，由N-乙酰基葡糖胺（GlcNAc）和N-乙酰基尿酸（MurNAc）的交替单元组成的其聚合结构也是宿主防御酶如溶菌酶的作用的靶标。许多细菌已经开发出通过添加糖苷配基部分来掩盖其细胞壁免受这些环境危害的方法，所述糖苷配基部分阻止识别或在空间上阻碍外源酶的降解作用，否则会损害细胞。肽聚糖乙酰基转移酶（Pat's）和O-乙酰基肽聚糖酯酶（Ape's）是负责将乙酸盐控制添加到肽聚糖中MurNAc残基的C-6羟基上并从中去除的酶。对淋病奈瑟氏菌中发现的一种O-乙酰基肽聚糖酯酶Ape1的研究表明，该酶对于细菌生存力是必不可少的，因此为抗菌设计提出了一个有吸引力的目标。由于Ape1的天然底物是不溶性聚合物，因此以前对Ape1的研究受到了阻碍。在本文中，我们概述了水溶性二糖和单糖底物类似物1和2的设计，合成和测试。既1和2作为与APE1的基板k