6-O-(6-aminocaproyl)-2,3-di-O-benzyl-L-ascorbic acid trifluoroacetic salt

• 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: 6-O-(6-aminocaproyl)-2,3-di-O-benzyl-L-ascorbic acid trifluoroacetic salt
• 英文别名: [(2S)-2-hydroxy-2-[(2R)-5-oxo-3,4-bis(phenylmethoxy)-2H-furan-2-yl]ethyl] 6-aminohexanoate;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₂₆H₃₁NO₇
• 分子量: 583.559
• InChiKey: RLEXPMXYIVJTRW-ITOBZAKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.61
• 重原子数：
  41
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  155
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  6-O-(6-aminocaproyl)-2,3-di-O-benzyl-L-ascorbic acid trifluoroacetic salt 在 Pearlman's catalyst 、 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以85%的产率得到[(2S)-2-[(2R)-3,4-dihydroxy-5-oxo-2H-furan-2-yl]-2-hydroxyethyl] 6-aminohexanoate;2,2,2-trifluoroacetic acid
  参考文献：
  名称：

  Potential Neuroprotective Drugs in Cerebral Ischemia: New Saturated and Polyunsaturated Lipids Coupled to Hydrophilic Moieties: Synthesis and Biological Activity

  摘要：

  The ganglioside GM1 has neuroprotective effects but is not of therapeutic value because of its lack of bioavailability. Thus, molecules that mimic GM I represent a novel approach to neuroprotection. We have synthesized 19 small GM1-like analogues whose simplified structure includes a hydrophobic saturated or unsaturated moiety linked to a hydrophilic moiety. We report their neuroprotective effects in two distinct models of nerve cell death using hippocampus-derived HT22 cells. We found that several analogues protected the HT22 cells from death at concentrations ranging from 2 to 5 mu M. Additional neuroprotective assays using cortical slices injured by glutamate confirmed these results. Since members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the GM1-like analogues. Interestingly, the results indicate that the compounds provide neuroprotection through distinct mechanisms of action.

  DOI：

  10.1021/jm900227u
• 作为产物：
  描述：

  [(2S)-2-hydroxy-2-[(2R)-5-oxo-3,4-bis(phenylmethoxy)-2H-furan-2-yl]ethyl] 6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate 、 三氟乙酸 以 二氯甲烷 为溶剂， 以0.84 g的产率得到6-O-(6-aminocaproyl)-2,3-di-O-benzyl-L-ascorbic acid trifluoroacetic salt
  参考文献：
  名称：

  Potential Neuroprotective Drugs in Cerebral Ischemia: New Saturated and Polyunsaturated Lipids Coupled to Hydrophilic Moieties: Synthesis and Biological Activity

  摘要：

  The ganglioside GM1 has neuroprotective effects but is not of therapeutic value because of its lack of bioavailability. Thus, molecules that mimic GM I represent a novel approach to neuroprotection. We have synthesized 19 small GM1-like analogues whose simplified structure includes a hydrophobic saturated or unsaturated moiety linked to a hydrophilic moiety. We report their neuroprotective effects in two distinct models of nerve cell death using hippocampus-derived HT22 cells. We found that several analogues protected the HT22 cells from death at concentrations ranging from 2 to 5 mu M. Additional neuroprotective assays using cortical slices injured by glutamate confirmed these results. Since members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the GM1-like analogues. Interestingly, the results indicate that the compounds provide neuroprotection through distinct mechanisms of action.

  DOI：

  10.1021/jm900227u

文献信息

• Design of β-Secretase Inhibitors by Introduction of a Mandelyl Moiety in DAPT Analogues
  作者：Nicolas Pietrancosta、Gilles Quéléver、Younes Laras、Cédrik Garino、Stéphane Burlet、Jean Louis Kraus

  DOI：10.1071/ch05102

  日期：——

  We report the synthesis of two series of compounds with 3,5-difluoromandelyl-alanyl or 3,5-difluorophenylacetyl-alanyl backbones coupled to various heterocyclic or peptidic moieties. These two series of compounds were evaluated for their inhibitory properties on β-secretase (BACE-1) enzymatic assay, a target enzyme for Alzheimer’s disease (AD) pathology. We found that both diastereomers obtained from the racemic mixture 7 of the coumarin derivative bearing a mandelyl moiety were the most potent BACE-1 inhibitors studied in this work (IC50 = 1 × 10−6 M). Analysis of the obtained results led to the hypothesis that introduction of a difluoromandelyl residue in place of a difluorophenylacetyl moiety may induce β-secretase inhibitory activity.

  我们报告了以 3,5-二氟甲酰基丙氨酰或 3,5-二氟苯乙酰基丙氨酰为骨架、与各种杂环或肽基偶联的两个系列化合物的合成。我们评估了这两个系列的化合物对阿尔茨海默病（AD）病理靶酶 β-分泌酶（BACE-1）的抑制特性。我们发现，从带有曼地尔分子的香豆素衍生物的外消旋混合物 7 中得到的两种非对映异构体都是本研究中最有效的 BACE-1 抑制剂（IC50 = 1 × 10-6 M）。对所得结果进行分析后得出的假设是，引入二氟曼丁酰残基取代二氟苯乙酰基可能会诱导β-分泌酶抑制活性。
• Potential Neuroprotective Drugs in Cerebral Ischemia: New Saturated and Polyunsaturated Lipids Coupled to Hydrophilic Moieties: Synthesis and Biological Activity
  作者：Alain César Biraboneye、Sébastien Madonna、Younes Laras、Slavica Krantic、Pamela Maher、Jean-Louis Kraus

  DOI：10.1021/jm900227u

  日期：2009.7.23

  The ganglioside GM1 has neuroprotective effects but is not of therapeutic value because of its lack of bioavailability. Thus, molecules that mimic GM I represent a novel approach to neuroprotection. We have synthesized 19 small GM1-like analogues whose simplified structure includes a hydrophobic saturated or unsaturated moiety linked to a hydrophilic moiety. We report their neuroprotective effects in two distinct models of nerve cell death using hippocampus-derived HT22 cells. We found that several analogues protected the HT22 cells from death at concentrations ranging from 2 to 5 mu M. Additional neuroprotective assays using cortical slices injured by glutamate confirmed these results. Since members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the GM1-like analogues. Interestingly, the results indicate that the compounds provide neuroprotection through distinct mechanisms of action.