N-[(2R,3R,4R,5R,6R)-2-(2-Azido-ethoxy)-4,5-dihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-yl]-2,2,2-trifluoro-acetamide | 804557-80-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-[(2R,3R,4R,5R,6R)-2-(2-Azido-ethoxy)-4,5-dihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-yl]-2,2,2-trifluoro-acetamide
• 英文别名: N-[(2R,3R,4R,5R,6R)-2-(2-azidoethoxy)-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]-2,2,2-trifluoroacetamide
• CAS: 804557-80-0
• 化学式: C₁₀H₁₅F₃N₄O₆
• 分子量: 344.248
• InChiKey: GGLIYQAQCDJSTH-JAJWTYFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  123
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N-[(2R,3R,4R,5R,6R)-2-(2-Azido-ethoxy)-4,5-dihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-yl]-2,2,2-trifluoro-acetamide 在 sodium hydroxide 作用下， 生成 (2R,3R,4R,5R,6R)-5-amino-6-(2-azidoethoxy)-2-(hydroxymethyl)oxane-3,4-diol
  参考文献：
  名称：

  A Chemoenzymatic Approach to Glycopeptide Antibiotics

  摘要：

  Many biologically active natural products are constrained by macrocyclization and modified with carbohydrates. These two types of modifications are essential for their biological activities. Here we report a chemoenzymatic approach to make carbohydrate-modified cyclic peptide antibiotics. Using a thioesterase domain from the decapeptide tyrocidine synthetase, 13 head-to-tail cyclized tyrocidine derivatives were obtained with one to three propargylglycines incorporated at positions 3-8. These cyclic peptides were then conjugated to 21 azido sugars via copper(I)-catalyzed cycloaddition. Antibacterial and hemolytic assays showed that the two best glycopeptides, Tyc4PG-14 and Tyc4PG-15, have a 6-fold better therapeutic index than the natural tyrocidine. We believe this method will also be useful for modifying other natural products to search for new therapeutics.

  DOI：

  10.1021/ja045147v
• 作为产物：
  描述：

  1,3,4,6-tetra-O-acetyl-2-deoxy-2-trifluoroacetamido-β-D-galactopyranoside 在 甲醇 、 三氟化硼乙醚 、 sodium methylate 作用下， 以 二氯甲烷 为溶剂， 生成 N-[(2R,3R,4R,5R,6R)-2-(2-Azido-ethoxy)-4,5-dihydroxy-6-hydroxymethyl-tetrahydro-pyran-3-yl]-2,2,2-trifluoro-acetamide
  参考文献：
  名称：

  A Chemoenzymatic Approach to Glycopeptide Antibiotics

  摘要：

  Many biologically active natural products are constrained by macrocyclization and modified with carbohydrates. These two types of modifications are essential for their biological activities. Here we report a chemoenzymatic approach to make carbohydrate-modified cyclic peptide antibiotics. Using a thioesterase domain from the decapeptide tyrocidine synthetase, 13 head-to-tail cyclized tyrocidine derivatives were obtained with one to three propargylglycines incorporated at positions 3-8. These cyclic peptides were then conjugated to 21 azido sugars via copper(I)-catalyzed cycloaddition. Antibacterial and hemolytic assays showed that the two best glycopeptides, Tyc4PG-14 and Tyc4PG-15, have a 6-fold better therapeutic index than the natural tyrocidine. We believe this method will also be useful for modifying other natural products to search for new therapeutics.

  DOI：

  10.1021/ja045147v

文献信息

• A Chemoenzymatic Approach to Glycopeptide Antibiotics
  作者：Hening Lin、Christopher T. Walsh

  DOI：10.1021/ja045147v

  日期：2004.11.1

  Many biologically active natural products are constrained by macrocyclization and modified with carbohydrates. These two types of modifications are essential for their biological activities. Here we report a chemoenzymatic approach to make carbohydrate-modified cyclic peptide antibiotics. Using a thioesterase domain from the decapeptide tyrocidine synthetase, 13 head-to-tail cyclized tyrocidine derivatives were obtained with one to three propargylglycines incorporated at positions 3-8. These cyclic peptides were then conjugated to 21 azido sugars via copper(I)-catalyzed cycloaddition. Antibacterial and hemolytic assays showed that the two best glycopeptides, Tyc4PG-14 and Tyc4PG-15, have a 6-fold better therapeutic index than the natural tyrocidine. We believe this method will also be useful for modifying other natural products to search for new therapeutics.