(2S,3S,4R,5R)-2-Phenethylpiperidine-3,4,5-triol | 1604817-02-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: (2S,3S,4R,5R)-2-Phenethylpiperidine-3,4,5-triol
• 英文别名: (5S)-5-C-(2-phenylethyl)-1,5-dideoxy-1,5-imino-L-ribitol；(2S,3S,4R,5R)-2-(2-phenylethyl)piperidine-3,4,5-triol
• CAS: 1604817-02-8
• 化学式: C₁₃H₁₉NO₃
• 分子量: 237.299
• InChiKey: SLLXJYHZWHGLMV-QNWHQSFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  72.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  benzyl (5S,S_RS)-5-tert-butanesulfinamido-5-deoxy-5-C-(2-phenylethyl)-2,3-O-isopropylidene-β-L-ribofuranoside 在 甲醇 、 palladium 10% on activated carbon 、 水 、 氢气 、 溶剂黄146 、 乙酰氯 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 72.0h， 生成 (2S,3S,4R,5R)-2-Phenethylpiperidine-3,4,5-triol
  参考文献：
  名称：

  N-Alkyl-, 1-C-Alkyl-, and 5-C-Alkyl-1,5-dideoxy-1,5-imino-(l)-ribitols as Galactosidase Inhibitors

  摘要：

  AbstractA series of 1,5‐dideoxy‐1,5‐imino‐(l)‐ribitol (DIR) derivatives carrying alkyl or functionalized alkyl groups were prepared and investigated as glycosidase inhibitors. These compounds were designed as simplified 4‐epi‐isofagomine (4‐epi‐IFG) mimics and were expected to behave as selective inhibitors of β‐galactosidases. All compounds were indeed found to be highly selective for β‐galactosidases versus α‐glycosidases, as they generally did not inhibit coffee bean α‐galactosidase or other α‐glycosidases. Some compounds were also found to be inhibitors of almond β‐glucosidase. The N‐alkyl DIR derivatives were only modest inhibitors of bovine β‐galactosidase, with IC50 values in the 30–700 μm range. Likewise, imino‐l‐ribitol substituted at the C1 position was found to be a weak inhibitor of this enzyme. In contrast, alkyl substitution at C5 resulted in enhanced β‐galactosidase inhibitory activity by a factor of up to 1000, with at least six carbon atoms in the alkyl substituent. Remarkably, the ‘pseudo‐anomeric’ configuration in this series does not appear to play a role. Human lysosomal β‐galactosidase from leukocyte lysate was, however, poorly inhibited by all iminoribitol derivatives tested (IC50 values in the 100 μm range), while 4‐epi‐IFG was a good inhibitor of this enzyme. Two compounds were evaluated as pharmacological chaperones for a GM1‐gangliosidosis cell line (R301Q mutation) and were found to enhance the mutant enzyme activity by factors up to 2.7‐fold.

  DOI：

  10.1002/cmdc.201500485

文献信息

• Synthesis of 1,5-Dideoxy-1,5-iminoribitol <i>C</i>-Glycosides through a Nitrone–Olefin Cycloaddition Domino Strategy: Identification of Pharmacological Chaperones of Mutant Human Lysosomal β-Galactosidase
  作者：Aloysius Siriwardena、Dhiraj P. Sonawane、Omprakash P. Bande、Pramod R. Markad、Sayuri Yonekawa、Michael B. Tropak、Sougata Ghosh、Balu A. Chopade、Don J. Mahuran、Dilip D. Dhavale

  DOI：10.1021/jo500328u

  日期：2014.5.16

  that facilitates the synthesis of new 1,5-dideoxy-1,5-iminoribitol iminosugar C-glycosides 7a–e and 8. The key intermediate in this approach is a six-membered cyclic sugar nitrone that is generated in situ and trapped by an alkene dipolarophile via a [2 + 3] cycloaddition reaction to give the corresponding isooxazolidines 10a–e in a “one-pot” protocol. The iminoribitol C-glycosides 7a–e and 8 were found

  我们在这里报告了一种新开发的多米诺反应，它促进了新的1,5-二脱氧-1,5-亚氨基核糖醇亚氨基糖C-糖苷7a - e和8的合成。该方法的关键中间体是六元环糖硝酮，它是原位生成的，并由烯烃双极性亲和剂通过[2 + 3]环加成反应捕获，从而以“一锅法”提供相应的异恶唑烷10a – e。发现亚氨基核糖醇C-糖苷7a - e和8是适度的β-半乳糖苷酶（bGal）抑制剂。但是，化合物7c和7e 在突变型溶酶体bGal活性中显示出“药理伴侣”活性，并使其在GM1神经节病患者成纤维细胞中的恢复提高了2-6倍。
• <i>N</i>-Alkyl-, 1-<i>C</i>-Alkyl-, and 5-<i>C</i>-Alkyl-1,5-dideoxy-1,5-imino-(<scp>l</scp>)-ribitols as Galactosidase Inhibitors
  作者：Sophie Front、Estelle Gallienne、Julie Charollais-Thoenig、Stéphane Demotz、Olivier R. Martin

  DOI：10.1002/cmdc.201500485

  日期：2016.1

  AbstractA series of 1,5‐dideoxy‐1,5‐imino‐(l)‐ribitol (DIR) derivatives carrying alkyl or functionalized alkyl groups were prepared and investigated as glycosidase inhibitors. These compounds were designed as simplified 4‐epi‐isofagomine (4‐epi‐IFG) mimics and were expected to behave as selective inhibitors of β‐galactosidases. All compounds were indeed found to be highly selective for β‐galactosidases versus α‐glycosidases, as they generally did not inhibit coffee bean α‐galactosidase or other α‐glycosidases. Some compounds were also found to be inhibitors of almond β‐glucosidase. The N‐alkyl DIR derivatives were only modest inhibitors of bovine β‐galactosidase, with IC50 values in the 30–700 μm range. Likewise, imino‐l‐ribitol substituted at the C1 position was found to be a weak inhibitor of this enzyme. In contrast, alkyl substitution at C5 resulted in enhanced β‐galactosidase inhibitory activity by a factor of up to 1000, with at least six carbon atoms in the alkyl substituent. Remarkably, the ‘pseudo‐anomeric’ configuration in this series does not appear to play a role. Human lysosomal β‐galactosidase from leukocyte lysate was, however, poorly inhibited by all iminoribitol derivatives tested (IC50 values in the 100 μm range), while 4‐epi‐IFG was a good inhibitor of this enzyme. Two compounds were evaluated as pharmacological chaperones for a GM1‐gangliosidosis cell line (R301Q mutation) and were found to enhance the mutant enzyme activity by factors up to 2.7‐fold.