1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridyl-3-methanol | 215725-60-3

• 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: 1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridyl-3-methanol
• 英文别名: tert-butyl 5-(hydroxymethyl)-5,6-dihydropyridine-1(2H)-carboxylate；tert-butyl 3-(hydroxymethyl)-3,6-dihydro-2H-pyridine-1-carboxylate
• CAS: 215725-60-3
• 化学式: C₁₁H₁₉NO₃
• 分子量: 213.277
• InChiKey: KJKIBMLLPGCGOZ-UHFFFAOYSA-N

物化性质

• 沸点：
  310.9±35.0 °C(Predicted)
• 密度：
  1.085±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridyl-3-methanol 在 氢氧化钾 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 生成 (3S,4S,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine
  参考文献：
  名称：

  Iminosugars: potential inhibitors of liver glycogen phosphorylase

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(00)00291-1
• 作为产物：
  描述：

  槟榔碱 在 锂硼氢 、 1-氯乙基氯甲酸酯 、 三乙基硼氢化锂 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 甲苯 为溶剂， 反应 4.58h， 生成 1-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridyl-3-methanol
  参考文献：
  名称：

  Iminosugars: potential inhibitors of liver glycogen phosphorylase

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(00)00291-1

文献信息

• Ligand-Controlled Regiodivergent Nickel-Catalyzed Annulation of Pyridones
  作者：Pavel A. Donets、Nicolai Cramer

  DOI：10.1002/anie.201409669

  日期：2014.11.6

  The 1,6‐annulated 2‐pyridone motif is found in many biologically active compounds and its close relation to the indolizidine and quinolizidine alkaloid core makes it an attractive building block. A nickel‐catalyzed CH functionalization of 2‐pyridones and subsequent cyclization affords 1,6‐annulated 2‐pyridones by selective intramolecular olefin hydroarylation. The switch between the exo‐ and endo‐cyclization

  在许多具有生物活性的化合物中均存在1,6-环化的2-吡啶酮基序，它与吲哚并立定和喹喔啉碱生物碱核心密切相关，使其成为有吸引力的构建基块。镍-催化的Ç 通过选择性分子内烯烃hydroarylation的2-吡啶酮和随后的环化，得到ħ官能1,6-环化2-吡啶酮。之间的开关外切和内切-cyclization模式是由两个互补的套配体的控制。不论环的大小如何，环化过程中的区域选择性都在催化剂的完全控制下。简单环辛二烯促进一个外切-选择性环化，而在一个大体积的N-杂环卡宾配体结果内切选择性模式。该方法进一步应用于羽扇豆生物碱的胱氨酸的合成。