N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl)-L-serine benzyl ester | 1174725-59-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl)-L-serine benzyl ester
• 英文别名: Fmoc-L-Ser(GlcNAcα)OBn；benzyl (2S)-3-[(2S,3R,4R,5S,6R)-3-acetamido-4,5-diacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoate
• CAS: 1174725-59-7
• 化学式: C₃₉H₄₂N₂O₁₃
• 分子量: 746.768
• InChiKey: YFHLTVVKNQMZBT-ZGZQXUDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  54
• 可旋转键数：
  19
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  191
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl)-L-serine benzyl ester 在 palladium on activated charcoal 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 甲酸 、 水 为溶剂， 反应 2.0h， 以73%的产率得到N-(9-fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-α-D-glucopyranosyl)-L-serine
  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：

  3-巯基丙酸 、 N-(9-fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-glucopyranosyl)-L-serine benzyl ester 在 吡啶 作用下， 以97%的产率得到N-[(9H-fluoren-9-ylmethoxy)carbonyl]-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl)-L-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

文献信息

• Novel and facile solution-phase synthesis of 2,5-diketopiperazines and O-glycosylated analogs
  作者：Vanessa L. Campo、Maristela B. Martins、Carlos H.T.P. da Silva、Ivone Carvalho

  DOI：10.1016/j.tet.2009.04.069

  日期：2009.7

  This work describes the synthesis in Solution of a series of related diketopiperazines with potential biological activities: cyclo(L-Pro-L-Ser), cyclo(L-Phe-L-Ser), cyclo(D-Phe-L-Ser) and the corresponding glycosylated analogs of the latter, cyclo[D-Phe-L-Ser(alpha GlcNAc)] and cyclo[D-Phe-L-Ser(beta GlcNAc)]. The synthetic approach involved coupling reactions of -OH or O-glycosylated serine benzyl esters with NFmoc-protected amino acids (Pro or Phe), followed by one-pot deprotection-cyclization reaction in the presence of 20% piperidine in DMF. (C) 2009 Elsevier Ltd. All rights reserved.