N-(9H-fluoren-9-ylmethoxycarbonyl)-O-(2-azido-2-deoxy-3,4,6-tri-O-α-D-galactopyranosyl)-D-serine benzyl ester | 1370339-04-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-(9H-fluoren-9-ylmethoxycarbonyl)-O-(2-azido-2-deoxy-3,4,6-tri-O-α-D-galactopyranosyl)-D-serine benzyl ester
• CAS: 1370339-04-0
• 化学式: C₃₇H₃₈N₄O₁₂
• 分子量: 730.728
• InChiKey: VHSPPZUCLPLXIM-MWLYIGDASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.48
• 重原子数：
  53.0
• 可旋转键数：
  14.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  210.75
• 氢给体数：
  1.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  3-巯基丙酸 、 N-(9H-fluoren-9-ylmethoxycarbonyl)-O-(2-azido-2-deoxy-3,4,6-tri-O-α-D-galactopyranosyl)-D-serine benzyl ester 在 吡啶 作用下， 以73%的产率得到N-(9H-fluoren-9-ylmethoxycarbonyl)-O-(2-acetyl-2-deoxy-3,4,6-tri-O-α-D-galactopyranosyl)-D-serine benzyl ester
  参考文献：
  名称：

  Enhanced Epimerization of Glycosylated Amino Acids During Solid-Phase Peptide Synthesis

  摘要：

  Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In this study, we demonstrate that many common peptide coupling conditions used to prepare O-linked glycopeptides result in substantial amounts of epimerization at the a position. In fact, epimerization resulted in up to 80% of the non-natural epimer, indicating that it can be the major product in some reactions. Through a series of mechanistic studies, we demonstrate that the enhanced epimerization relative to nonglycosylated amino acids is due to a combination of factors, including a faster rate of epimerization, an energetic preference for the unnatural epimer over the natural epimer, and a slower overall rate of peptide coupling. In addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization. The information and improved reaction conditions will facilitate the preparation of glycopeptides as therapeutic compounds and vaccine antigens.

  DOI：

  10.1021/ja212188r
• 作为产物：
  描述：

  N-(9H-fluoren-9-ylmethoxycarbonyl)-D-serine benzyl ester 、 3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-galactopyranosyl bromide 在 silver perchlorate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以60%的产率得到N-(9H-fluoren-9-ylmethoxycarbonyl)-O-(2-azido-2-deoxy-3,4,6-tri-O-α-D-galactopyranosyl)-D-serine benzyl ester
  参考文献：
  名称：

  Enhanced Epimerization of Glycosylated Amino Acids During Solid-Phase Peptide Synthesis

  摘要：

  Glycopeptides are extremely useful for basic research and clinical applications, but access to structurally defined glycopeptides is limited by the difficulties in synthesizing this class of compounds. In this study, we demonstrate that many common peptide coupling conditions used to prepare O-linked glycopeptides result in substantial amounts of epimerization at the a position. In fact, epimerization resulted in up to 80% of the non-natural epimer, indicating that it can be the major product in some reactions. Through a series of mechanistic studies, we demonstrate that the enhanced epimerization relative to nonglycosylated amino acids is due to a combination of factors, including a faster rate of epimerization, an energetic preference for the unnatural epimer over the natural epimer, and a slower overall rate of peptide coupling. In addition, we demonstrate that use of 2,4,6-trimethylpyridine (TMP) as the base in peptide couplings produces glycopeptides with high efficiency and low epimerization. The information and improved reaction conditions will facilitate the preparation of glycopeptides as therapeutic compounds and vaccine antigens.

  DOI：

  10.1021/ja212188r