N-tert-butoxycarbonyl-(3R,4S,5R)-4-hydroxy-5-hydroxymethyl-3-piperidinecarboxylic methyl ester | 309918-21-6

• 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: N-tert-butoxycarbonyl-(3R,4S,5R)-4-hydroxy-5-hydroxymethyl-3-piperidinecarboxylic methyl ester
• 英文别名: (3R,4S,5R)-N-tert-butyloxycarbonyl-4-hydroxy-5-hydroxymethyl-piperidine-3-carboxylic acid methyl ester；1-O-tert-butyl 3-O-methyl (3R,4S,5R)-4-hydroxy-5-(hydroxymethyl)piperidine-1,3-dicarboxylate
• CAS: 309918-21-6
• 化学式: C₁₃H₂₃NO₆
• 分子量: 289.329
• InChiKey: NSPLFGOHHKMTAL-BBBLOLIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  96.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-tert-butoxycarbonyl-(3R,4S,5R)-4-hydroxy-5-hydroxymethyl-3-piperidinecarboxylic methyl ester 在 lithium hydroxide 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 22.0h， 生成 (3R,4S,5R)-N-tert-butyloxycarbonyl-4-hydroxy-5-hydroxymethyl-4,5'-O-isopropylidene-piperidine-3-carboxylic acid
  参考文献：
  名称：

  Chemoenzymatic Synthesis of Isogalactofagomine

  摘要：

  A new chemoenzymatic synthesis of optically pure isogalactofagomine 2 starting from achiral starting materials is presented. Dimethyl 4-hydroxypyridine-3,5-dicarboxylate (7) was synthesized and converted to the corresponding saturated piperidine 8. Then the key step of the synthesis was carried out: Lipase M catalyzed hydrolysis of the prochiral diester 8 to cause formation of an asymmetric monoacid with at least 98% enantiomeric excess. Reduction of the acid, saponification of the remaining ester, and radical iododecarboxylation gave an iodide that after substitution with silver trifluoroacetate and hydrolysis gave 2.

  DOI：

  10.1021/jo000699r
• 作为产物：
  描述：

  (3,4-cis-4,5-cis)-N-tert-butyloxycarbonyl-4-hydroxypiperidine-3,5-dicarboxylic acid dimethyl ester 在 硼烷四氢呋喃络合物 、 Murcor javanicus lipase M 作用下， 以 四氢呋喃 、 phosphate buffer 为溶剂， 反应 73.0h， 生成 N-tert-butoxycarbonyl-(3R,4S,5R)-4-hydroxy-5-hydroxymethyl-3-piperidinecarboxylic methyl ester
  参考文献：
  名称：

  Chemoenzymatic Synthesis of Isogalactofagomine

  摘要：

  A new chemoenzymatic synthesis of optically pure isogalactofagomine 2 starting from achiral starting materials is presented. Dimethyl 4-hydroxypyridine-3,5-dicarboxylate (7) was synthesized and converted to the corresponding saturated piperidine 8. Then the key step of the synthesis was carried out: Lipase M catalyzed hydrolysis of the prochiral diester 8 to cause formation of an asymmetric monoacid with at least 98% enantiomeric excess. Reduction of the acid, saponification of the remaining ester, and radical iododecarboxylation gave an iodide that after substitution with silver trifluoroacetate and hydrolysis gave 2.

  DOI：

  10.1021/jo000699r

文献信息

• Stereoelectronic Substituent Effects in Polyhydroxylated Piperidines and Hexahydropyridazines
  作者：Henrik Helligsø Jensen、Laila Lyngbye、Astrid Jensen、Mikael Bols

  DOI：10.1002/1521-3765(20020301)8:5<1218::aid-chem1218>3.0.co;2-x

  日期：2002.3.1

  group in the 4-position relative to the amine were 0.4 pH units more acidic than the corresponding compound with an axial OH. A similar effect was observed for the COOMe substituent. The difference in electron-withdrawing power of axial and equatorial substituents was explained by a difference in charge-dipole interactions in the two systems. Since this stereoelectronic substituent effect causes differences

  从大量的羟基化哌啶和六氢哒嗪的共轭酸的pK（a）值，发现在具有轴向或赤道羟基（OH）基团（相对于胺而言）的立体异构体之间，碱度存在一致的差异。与其他相同的具有轴向OH基团的化合物相比，在3位具有赤道OH基团的化合物的酸度高0.8个pH单位，而相对于胺在4位具有赤道OH基团的化合物的酸度比其他的酸碱度高0.4个pH单位。带有轴向OH的相应化合物。对于COOMe取代基观察到类似的效果。轴向和赤道取代基的吸电子能力的差异是由两个系统中电荷-偶极相互作用的差异解释的。由于这种立体电子取代基效应导致不同构象异构体的碱性不同，因此发现某些哌啶和六氢哒嗪在质子化时会改变构象。描述了一种预测立体异构体的哌啶的pK（a）的方法。
• A bioisosteric oligosaccharide mimetic based on isofagomine-type monomers
  作者：Xifu Liang、Bent O. Petersen、Jens Ø. Duus、Mikael Bols

  DOI：10.1039/b103756k

  日期：2001.11.1

  A series of hydroxylated piperidine oligomers that resemble oligosaccharides is synthesised. Prepared were 5, a mimic of 3-O-L-fucopyranosyl-D-galactopyranose, 6, a mimic of 3-O-D-galactopyranosyl-D-galactopyranose and 7, a mimic of 3-O-3-O-[3-O-(L-fucopyranosyl)-D-galactopyranosyl]-D-galactopyranosyl}-D-galactopyranose. Conformational analysis of the new compounds using NMR spectroscopy showed them to have predominant conformations that were similar to those adopted by β-O-glycosides. The inhibition of a series of glycosidases by 5–7 was investigated and found to be inferior to that of the corresponding unsubstituted isofagomines.

  合成了一系列类似于寡糖的羟基化哌啶低聚物。制备了5个，3-O-L-吡喃岩藻糖基-D-吡喃半乳糖的模拟物，6个，3-O-D-吡喃半乳糖基-D-吡喃半乳糖的模拟物和7个，3-O-D-吡喃半乳糖基-D-吡喃半乳糖的模拟物3-O-3-O-[3-O-(L-吡喃岩藻糖基)-D-吡喃半乳糖基]-D-吡喃半乳糖基}-D-吡喃半乳糖。使用核磁共振波谱对新化合物进行构象分析表明，它们具有与 β-O-糖苷相似的主要构象。对 5-7 一系列糖苷酶的抑制作用进行了研究，发现其效果不如相应的未取代的异法戈明。
• Chemoenzymatic Synthesis of Isogalactofagomine
  作者：Xifu Liang、Anders Lohse、Mikael Bols

  DOI：10.1021/jo000699r

  日期：2000.11.1

  A new chemoenzymatic synthesis of optically pure isogalactofagomine 2 starting from achiral starting materials is presented. Dimethyl 4-hydroxypyridine-3,5-dicarboxylate (7) was synthesized and converted to the corresponding saturated piperidine 8. Then the key step of the synthesis was carried out: Lipase M catalyzed hydrolysis of the prochiral diester 8 to cause formation of an asymmetric monoacid with at least 98% enantiomeric excess. Reduction of the acid, saponification of the remaining ester, and radical iododecarboxylation gave an iodide that after substitution with silver trifluoroacetate and hydrolysis gave 2.