(1R,2S,6S)-2-((tert-butyldiphenylsilyloxy)methyl)-7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxyliac acid tert-butyl ester | 1314080-59-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1R,2S,6S)-2-((tert-butyldiphenylsilyloxy)methyl)-7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxyliac acid tert-butyl ester
• CAS: 1314080-59-5
• 化学式: C₂₇H₃₇NO₄Si
• 分子量: 467.681
• InChiKey: WXXNKCCQKDHGPV-KMDXXIMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.34
• 重原子数：
  33.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  51.3
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (1R,2S,6S)-2-((tert-butyldiphenylsilyloxy)methyl)-7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxyliac acid tert-butyl ester 在 硫酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以80%的产率得到(2S,3S,4S)-2-(hydroxymethyl)piperidine-3,4-diol
  参考文献：
  名称：

  Docking and SAR studies of d- and l-isofagomine isomers as human β-glucocerebrosidase inhibitors

  摘要：

  We report the structure-activity relationship of a series of D-, and L-isofagomine and fagomine isomers as glycosidase inhibitors. Our study revealed that a positive charge at the anomeric position of D-isofagomines enhanced the potency toward beta-glycosidases, while the epimerization at the C3 OH group drastically reduced their inhibitory potency by over three orders of magnitude. Furthermore, D-3,4-di-epi-isofagomine abolished their inhibition activities against all enzymes. L-Isofagomine was also a fairly potent inhibitor of human beta-glucocerebrosidase, with an IC50 value of 8.7 mu M. A molecular docking study revealed that the positions and orientations of the piperidine ring of D-3-epi-isofagomine in the binding site was similar to that of D-isofagomine, while D-3-epi-isofagomine missed the hydrogen bond interactions between Asp127 and the 3-OH group and between Trp179 and the 3-OH group. Furthermore, the top 10 docking models ranked by IFDscore suggested that D-3,4-di-epi-isofagomine can not bind to beta-glucocerebrosidase at a stable interaction mode. These results provide an insight into the structural requirements of isofagomine isomers for developing a new type of pharmacological chaperone for Gaucher disease. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.011
• 作为产物：
  描述：

  tert-butyl (R)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-3,6-dihydropyridine-1(2H)-carboxylate 在 Oxone 、 1,1,1-三氟丙酮 、 edetate disodium 、 碳酸氢钠 作用下， 以 水 、 乙腈 为溶剂， 反应 1.5h， 以59%的产率得到(1R,2S,6S)-2-((tert-butyldiphenylsilyloxy)methyl)-7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxyliac acid tert-butyl ester
  参考文献：
  名称：

  Docking and SAR studies of d- and l-isofagomine isomers as human β-glucocerebrosidase inhibitors

  摘要：

  We report the structure-activity relationship of a series of D-, and L-isofagomine and fagomine isomers as glycosidase inhibitors. Our study revealed that a positive charge at the anomeric position of D-isofagomines enhanced the potency toward beta-glycosidases, while the epimerization at the C3 OH group drastically reduced their inhibitory potency by over three orders of magnitude. Furthermore, D-3,4-di-epi-isofagomine abolished their inhibition activities against all enzymes. L-Isofagomine was also a fairly potent inhibitor of human beta-glucocerebrosidase, with an IC50 value of 8.7 mu M. A molecular docking study revealed that the positions and orientations of the piperidine ring of D-3-epi-isofagomine in the binding site was similar to that of D-isofagomine, while D-3-epi-isofagomine missed the hydrogen bond interactions between Asp127 and the 3-OH group and between Trp179 and the 3-OH group. Furthermore, the top 10 docking models ranked by IFDscore suggested that D-3,4-di-epi-isofagomine can not bind to beta-glucocerebrosidase at a stable interaction mode. These results provide an insight into the structural requirements of isofagomine isomers for developing a new type of pharmacological chaperone for Gaucher disease. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.011