(3S)-1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridyl-3-methanol | 346408-34-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (3S)-1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridyl-3-methanol
• 英文别名: (S)-N-tert-butoxycarbonyl-5-(hydroxymethyl)-3-piperidene；tert-butyl (3S)-3-(hydroxymethyl)-3,6-dihydro-2H-pyridine-1-carboxylate
• CAS: 346408-34-2
• 化学式: C₁₁H₁₉NO₃
• 分子量: 213.277
• InChiKey: KJKIBMLLPGCGOZ-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  49.77
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (3S)-1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridyl-3-methanol 在 咪唑 、 4-二甲氨基吡啶 、 Oxone 、 1,1,1-三氟丙酮 、 水 、 edetate disodium 、 碳酸氢钠 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 3.0h， 生成
  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：

  (R)-N-tert-butoxycarbonyl-5-(tributylstannyl)methoxy-3-piperidene 在 正丁基锂 作用下， 以 正己烷 、 正戊烷 为溶剂， 反应 3.0h， 以65%的产率得到(3S)-1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridyl-3-methanol
  参考文献：
  名称：

  Asymmetric Synthesis of All Stereoisomers of Isofagomine Using [2,3]-Wittig Rearrangement

  摘要：

  DOI：

  10.3987/com-07-s(k)58

文献信息

• Iminosugars: potential inhibitors of liver glycogen phosphorylase
  作者：Palle Jakobsen、Jane M Lundbeck、Marit Kristiansen、Jens Breinholt、Helle Demuth、Jan Pawlas、Maria P Torres Candela、Birgitte Andersen、Niels Westergaard、Karsten Lundgren、Naoki Asano

  DOI：10.1016/s0968-0896(00)00291-1

  日期：2001.3

  The first synthesis of the single isomers (3R,4R,5R); (3S,4S,5S); (3R,4R,5S) and (3S,4S,5R) of 5-hydroxymethyl-piperidine-3,4-diol from Arecolin is reported, including the synthesis of a series of N-substituted derivatives of the (3R,4R,5R)-isomer (Isofagomine). The inhibitory effect of these isomers as well as of a series of N-substituted derivatives of the (3R,4R,SR)-isomer and selected hydroxypiperidine analogues on liver glycogen phosphorylase (GP) showed that the (3R,4R,5R) configuration was essential for obtaining an inhibitory effect at submicromolar concentration. The results also showed that all three hydroxy groups should be present and could not be substituted, nor were extra OH groups allowed if sub-micromolar inhibition should be obtained. Some inhibitory effect was retained for N-substituted derivatives of Isofagagomine; however, N-substitution always resulted in a loss of activity compared to the parent compound, IC50 values ranging from 1 to 100 muM were obtained for simple alkyl, arylalkyl and benzoylmethyl substituents. Furthermore, we found that it was not enough to assure inhibitory effect to have the (R,,R) configuration. Fagomine, the (2R,3R,4R)-2-hydroxymethylpiperidine-3,4-diol analogue, showed an IC50 value of 200 muM compared to 0.7 muM for Isofagomine. In addition, Isofagomine was able to prevent basal and glucagon stimulated glycogen degradation in cultured hepatocytes with IC50 values of 2-3 muM. (C) 2001 Elsevier Science Ltd. All rights reserved.