methyl (1R,3R,4R,5S)-5-acetamido-1-benzyloxy-4-(tertbutoxycarbonylamino)-3-(2-tosyloxyethoxy)-cyclohexane-1-carboxylate | 1257059-91-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (1R,3R,4R,5S)-5-acetamido-1-benzyloxy-4-(tertbutoxycarbonylamino)-3-(2-tosyloxyethoxy)-cyclohexane-1-carboxylate
• CAS: 1257059-91-8
• 化学式: C₃₁H₄₂N₂O₁₀S
• 分子量: 634.748
• InChiKey: HKTDWKHQMUCBFZ-GMVMSBRFSA-N

反应信息

• 作为反应物：
  描述：

  methyl (1R,3R,4R,5S)-5-acetamido-1-benzyloxy-4-(tertbutoxycarbonylamino)-3-(2-tosyloxyethoxy)-cyclohexane-1-carboxylate 在 sodium azide 、 15-冠醚-5 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 以83%的产率得到methyl (1R,3R,4R,5S)-5-acetamido-3-(2-azidoethoxy)-1-benzyloxy-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
• 作为产物：
  描述：

  methyl (1R,3R,4R,5S)-5-acetamido-1-benzyloxy-4-(tertbutoxycarbonylamino)-3-(2-hydroxyethoxy)-cyclohexane-1-carboxylate 、 对甲苯磺酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以84%的产率得到methyl (1R,3R,4R,5S)-5-acetamido-1-benzyloxy-4-(tertbutoxycarbonylamino)-3-(2-tosyloxyethoxy)-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