tert-butyl (2S,3S)-3-hydroxy-2-(hydroxymethyl)-3,6-dihydro-2H-pyridine-1-carboxylate | 792950-98-2

• 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: tert-butyl (2S,3S)-3-hydroxy-2-(hydroxymethyl)-3,6-dihydro-2H-pyridine-1-carboxylate
• CAS: 792950-98-2
• 化学式: C₁₁H₁₉NO₄
• 分子量: 229.276
• InChiKey: YAODMORNKQPYHX-IUCAKERBSA-N

物化性质

• 沸点：
  353.2±42.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 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：
  70
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,3S)-3-hydroxy-2-(hydroxymethyl)-3,6-dihydro-2H-pyridine-1-carboxylate 在 四氧化锇 、 四甲基乙二胺 、 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 (2S,3R,4S,5S)-2-(hydroxymethyl)piperidine-3,4,5-triol hydrochloride
  参考文献：
  名称：

  Synthesis of 1-deoxy-l-gulonojirimycin and 1-deoxy-l-talonojirimycin

  摘要：

  De novo synthesis of noncompetitive glycosidase inhibitors L-gulo-DNJ and L-talo-DNJ has been achieved in 9-10 steps starting from Garner's aldehyde. Key to the success of this procedure was the construction of the 2,3-unsaturated piperidine 14, which syn dihydroxylation under Kishi's and Donohoe's conditions led to the desired iminosugars. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.02.111
• 作为产物：
  描述：

  tert-butyl (2S,3S)-3-acetyloxy-2-(acetyloxymethyl)-3,6-dihydro-2H-pyridine-1-carboxylate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以100%的产率得到tert-butyl (2S,3S)-3-hydroxy-2-(hydroxymethyl)-3,6-dihydro-2H-pyridine-1-carboxylate
  参考文献：
  名称：

  Synthesis of 1-deoxy-l-gulonojirimycin and 1-deoxy-l-talonojirimycin

  摘要：

  De novo synthesis of noncompetitive glycosidase inhibitors L-gulo-DNJ and L-talo-DNJ has been achieved in 9-10 steps starting from Garner's aldehyde. Key to the success of this procedure was the construction of the 2,3-unsaturated piperidine 14, which syn dihydroxylation under Kishi's and Donohoe's conditions led to the desired iminosugars. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.02.111

文献信息

• Biological Properties of <scp>d</scp>- and <scp>l</scp>-1-Deoxyazasugars
  作者：Atsushi Kato、Noriko Kato、Erika Kano、Isao Adachi、Kyoko Ikeda、Liang Yu、Tadashi Okamoto、Yasunori Banba、Hidekazu Ouchi、Hiroki Takahata、Naoki Asano

  DOI：10.1021/jm0495881

  日期：2005.3.1

  L-Enantiomers of 1-deoxynojirimycin (DNJ), 1-deoxymannojirimycin (manno-DNJ), 1-deoxyallonojirimycin (allo-DNJ), 1-deoxyaltronojirimycin (altro-DNJ), 1-deoxygalactonojirimycin (galacto-DNJ), 1-deoxygulonojirimycin (gulo-DNJ), and 1-deoxyldonojirimycin (ido-DNJ) were prepared according to prior methods for the D-enantiomers. These enantiospecific syntheses established unambiguously the absolute configuration of naturally occurring DNJ, manno-DNJ, allo-DNJ, altro-DNJ, and gulo-DNJ. Although D-DNJ and D-galacto-DNJ are known to be powerful competitive inhibitors of alpha-glucosidase and alpha-galactosidase, respectively, with K-i values in the nM range, L-DNJ and L-galacto-DNJ were noncompetitive inhibitors of alpha-glucosidase and alpha-galactosidase, respectively, with K-i values in the PM range. However, the azasugar mimicking the structure of the terminal sugar moiety of the natural substrate is not always an inhibitor of the glycosidase responsible for the hydrolysis. D-manno-DNJ is known as a much better inhibitor of alpha-L-fucosidase than a-mannosidase, while L-allo-DNJ was a better inhibitor than D-manno-DNJ of alpha-mannosidase. L-galacto-DNJ can be regarded as the 6-hydroxylated derivative of deoxyfuconojirimycin (DFJ), which is a powerful inhibitor of alpha-L-fucosidase with a K-i value in the nM range. However, this replacement of the methyl group in DFJ by a hydroxymethyl group reduced its affinity by about 50-fold. This suggests that there is a hydrophobic region in or around the active site of alpha-L-fucosidase. It has been found that inhibitors of human lysosomal glycosidases have therapeutic potential for the corresponding lysosomal storage diseases (Nat. Med. 1999, 5, 112; Proc. Natl. Acad. Sci. USA, 2002, 99, 15428). Inhibition of human lysosomal glycosidases by the 1-deoxyazasugars synthesized was investigated. D-galacto-DNJ is a potent inhibitor of lysosomal alpha-galactosidase (IC50 = 90 nM) and is now being evaluated preclinically for its potential use in Fabry disease, while D-DNJ inhibiting alpha-glucosidase (IC50 = 40 nM) potently does not appear to become a potential therapeutic agent because of additional inhibitory activity toward glycoprotein processing alpha-glucosidases. On the other hand, although L-allo-DNJ is a moderate inhibitor of alpha-mannosidase (IC50 = 64 mu M), it may become a key compound for the drug design of potential therapeutic agents for alpha-mannosidosis.