2-(trimethylsilyl)ethyl (benzyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosynate)-(2->3)-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1->3)-2-deoxy-6-O-[(S)-1-ethoxycarbonyl-ethyl]-2-trichloroacetamido-β-D-galactopyranoside | 1123178-62-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(trimethylsilyl)ethyl (benzyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosynate)-(2->3)-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1->3)-2-deoxy-6-O-[(S)-1-ethoxycarbonyl-ethyl]-2-trichloroacetamido-β-D-galactopyranoside
• 英文别名: benzyl (2S,4S,5R,6R)-5-acetamido-4-acetyloxy-2-[(2R,3S,4S,5R,6R)-3,5-diacetyloxy-2-(benzoyloxymethyl)-6-[(2R,3R,4R,5R,6R)-2-[[(2S)-1-ethoxy-1-oxopropan-2-yl]oxymethyl]-3-hydroxy-5-[(2,2,2-trichloroacetyl)amino]-6-(2-trimethylsilylethoxy)oxan-4-yl]oxyoxan-4-yl]oxy-6-[(1S,2R)-1,2,3-triacetyloxypropyl]oxane-2-carboxylate
• CAS: 1123178-62-0
• 化学式: C₆₁H₈₁Cl₃N₂O₂₈Si
• 分子量: 1424.76
• InChiKey: WPODJTJQNVJABH-KUFRQSKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.56
• 重原子数：
  95
• 可旋转键数：
  39
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  380
• 氢给体数：
  3
• 氢受体数：
  28

反应信息

• 作为反应物：
  描述：

  2-(trimethylsilyl)ethyl (benzyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosynate)-(2->3)-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1->3)-2-deoxy-6-O-[(S)-1-ethoxycarbonyl-ethyl]-2-trichloroacetamido-β-D-galactopyranoside 在 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 苯 为溶剂， 反应 3.75h， 生成 2-(trimethylsilyl)ethyl (benzyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosynate)-(2->3)-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1->3)-2-acetamido-2-deoxy-6-O-[(S)-1-ethoxycarbonyl-ethyl]-β-D-galactopyranoside
  参考文献：
  名称：

  Examination of the Biological Role of the α(2→6)-Linked Sialic Acid in Gangliosides Binding to the Myelin-Associated Glycoprotein (MAG)

  摘要：

  The tetrasaccharide 1, a substructure of ganglioside GQ1b alpha, shows a remarkable affinity for the myelin-associated glycoprotein (MAG) and was therefore selected as starting point for a lead optimization program. In our search for structurally simplified and pharmacokinetically improved mimics of 1, modifications of the core disaccharide, the alpha(2 -> 3)- and the alpha(2 -> 6)-linked sialic acid were synthesized. Biphenylmethyl and (S)-lactate were identified as suitable replacements for the alpha(2 -> 6)-linked sialic acid. Combined with a core modification and the earlier found aryl amide substituent in the 9-position of the alpha(2 -> 3)-linked sialic acid, high affinity MAG antagonists were identified. All mimics were tested in a competitive target-based binding assay, providing relative inhibitory potencies (rlP). Compared to the reference tetrasaccharide 1, the rIPs of the most potent antagonists 59 and 60 are enhanced nearly 400-fold. Their K(D)s determined in surface plasmon resonance experiments are in the low micromolar range. These results are in semiquantitative agreement with molecular modeling studies. This new class of glycomimetics will allow to validate the role of MAG in the axon regeneration process.

  DOI：

  10.1021/jm801058n
• 作为产物：
  描述：

  、 (R)-2-(三氟甲基磺酰基氧基)丙酸乙酯 在 二正丁基氧化锡 、 cesium fluoride 作用下， 以 苯 、 乙二醇二甲醚 为溶剂， 反应 27.0h， 以83%的产率得到2-(trimethylsilyl)ethyl (benzyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosynate)-(2->3)-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1->3)-2-deoxy-6-O-[(S)-1-ethoxycarbonyl-ethyl]-2-trichloroacetamido-β-D-galactopyranoside
  参考文献：
  名称：

  Examination of the Biological Role of the α(2→6)-Linked Sialic Acid in Gangliosides Binding to the Myelin-Associated Glycoprotein (MAG)

  摘要：

  The tetrasaccharide 1, a substructure of ganglioside GQ1b alpha, shows a remarkable affinity for the myelin-associated glycoprotein (MAG) and was therefore selected as starting point for a lead optimization program. In our search for structurally simplified and pharmacokinetically improved mimics of 1, modifications of the core disaccharide, the alpha(2 -> 3)- and the alpha(2 -> 6)-linked sialic acid were synthesized. Biphenylmethyl and (S)-lactate were identified as suitable replacements for the alpha(2 -> 6)-linked sialic acid. Combined with a core modification and the earlier found aryl amide substituent in the 9-position of the alpha(2 -> 3)-linked sialic acid, high affinity MAG antagonists were identified. All mimics were tested in a competitive target-based binding assay, providing relative inhibitory potencies (rlP). Compared to the reference tetrasaccharide 1, the rIPs of the most potent antagonists 59 and 60 are enhanced nearly 400-fold. Their K(D)s determined in surface plasmon resonance experiments are in the low micromolar range. These results are in semiquantitative agreement with molecular modeling studies. This new class of glycomimetics will allow to validate the role of MAG in the axon regeneration process.

  DOI：

  10.1021/jm801058n