methyl (1R,3R,4R,5S)-5-azido-1-benzyloxy-3-benzoyloxy-4-(tert-butoxycarbonylamino)-cyclohexane-1-carboxylate | 1257059-84-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl (1R,3R,4R,5S)-5-azido-1-benzyloxy-3-benzoyloxy-4-(tert-butoxycarbonylamino)-cyclohexane-1-carboxylate
• CAS: 1257059-84-9
• 化学式: C₂₇H₃₂N₄O₇
• 分子量: 524.574
• InChiKey: BVRUVQAXRFIMTD-HRGDABNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.71
• 重原子数：
  38.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  148.92
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  methyl (1R,3R,4R,5S)-5-azido-1-benzyloxy-3-benzoyloxy-4-(tert-butoxycarbonylamino)-cyclohexane-1-carboxylate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以94%的产率得到methyl (1R,3R,4R,5S)-5-azido-1-benzyloxy-4-(tertbutoxycarbonylamino)-3-hydroxy-cyclohexane-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, biological evaluation, and modeling of a non-carbohydrate antagonist of the myelin-associated glycoprotein

  摘要：

  Broad modifications of various positions of the minimal natural epitope recognized by the myelin-associated glycoprotein (MAG), a blocker of regeneration of neurite injuries, produced sialosides with nanomolar affinities. However, important pharmacokinetic issues, for example, the metabolic stability of these sialosides, remain to be addressed. For this reason, the novel non-carbohydrate mimic 3 was designed and synthesized from (-)-quinic acid. For the design of 3, previously identified beneficial modifications of side chains of Neu5Ac were combined with the replacement of the ring oxygen by a methylene group and the substitution of the C(4)-OH by an acetamide. Although docking experiments to a homology model of MAG revealed that mimic 3 forms all but one of the essential hydrogen bonds identified for the earlier reported lead 2, its affinity was substantially reduced. Extensive molecular-dynamics simulation disclosed that the missing hydrogen bond of the former C(8)-OH leads to a change of the orientation of the side chain. As a consequence, an important hydrophobic contact is compromised leading to a loss of affinity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.027
• 作为产物：
  描述：

  methyl (1R,3R,4R,5R)-4,5-aziridino-3-benzoyloxy-1-benzyloxy-N-(tert-butoxycarbonyl)-cyclohexane-1-carboxylate 在 sodium azide 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以64%的产率得到methyl (1R,3R,4R,5S)-5-azido-1-benzyloxy-3-benzoyloxy-4-(tert-butoxycarbonylamino)-cyclohexane-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, biological evaluation, and modeling of a non-carbohydrate antagonist of the myelin-associated glycoprotein

  摘要：

  Broad modifications of various positions of the minimal natural epitope recognized by the myelin-associated glycoprotein (MAG), a blocker of regeneration of neurite injuries, produced sialosides with nanomolar affinities. However, important pharmacokinetic issues, for example, the metabolic stability of these sialosides, remain to be addressed. For this reason, the novel non-carbohydrate mimic 3 was designed and synthesized from (-)-quinic acid. For the design of 3, previously identified beneficial modifications of side chains of Neu5Ac were combined with the replacement of the ring oxygen by a methylene group and the substitution of the C(4)-OH by an acetamide. Although docking experiments to a homology model of MAG revealed that mimic 3 forms all but one of the essential hydrogen bonds identified for the earlier reported lead 2, its affinity was substantially reduced. Extensive molecular-dynamics simulation disclosed that the missing hydrogen bond of the former C(8)-OH leads to a change of the orientation of the side chain. As a consequence, an important hydrophobic contact is compromised leading to a loss of affinity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.027