1,5-dideoxy-1,5-imino-L-galactitol | 126663-71-6

• 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: 1,5-dideoxy-1,5-imino-L-galactitol
• 英文别名: 1,5-Didesoxy-1,5-imino-L-galactit；L-DGJ；(2S,3R,4S,5R)-2-Hydroxymethyl-piperidine-3,4,5-triol；(2S,3R,4S,5R)-2-(hydroxymethyl)piperidine-3,4,5-triol
• CAS: 126663-71-6
• 化学式: C₆H₁₃NO₄
• 分子量: 163.174
• InChiKey: LXBIFEVIBLOUGU-KCDKBNATSA-N

物化性质

• 沸点：
  361.1±42.0 °C(Predicted)
• 密度：
  1.456±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  93
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-溴壬烷 、 1,5-dideoxy-1,5-imino-L-galactitol 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2S,3R,4S,5R)-2-(hydroxymethyl)-1-nonylpiperidine-3,4,5-triol
  参考文献：
  名称：

  基于荧光偏振活性的蛋白质谱分析法在人类非溶酶体葡萄糖基神经酰胺酶的有效，选择性抑制剂的发现中。

  摘要：

  人非溶酶体葡萄糖基神经酰胺酶（GBA2）是控制糖脂水平的几种酶之一，其活性与几种人类疾病状态相关。迫切需要设计或发现选择性的GBA2抑制剂作为化学工具和潜在的治疗剂。在这里，我们描述了基于荧光偏振活性的蛋白质谱分析（FluoPol-ABPP）测定法的发展，该测定法可从350多种亚氨基糖文库中快速鉴定GBA2抑制剂。基于FluoPol-ABPP筛选的线索生成聚焦库，并针对与其他葡糖神经酰胺代谢酶，葡糖神经酰胺合酶（GCS），溶酶体葡糖神经酰胺酶（GBA）和胞质保留β-葡糖苷酶GBA3的GBA2选择性偏移进行评估。我们的工作产生了有效的和选择性的GBA2抑制剂，

  DOI：

  10.1021/jacs.7b07352
• 作为产物：
  描述：

  3,4,5-Tri-O-benzoyl-2,6-didesoxy-2,6-imino-D-galactose-trimethylendithioacetal 在 Pd-Mohr 盐酸 、 甲醇 、 sodium tetrahydroborate 、 无水碳酸镉 、 氢气 、 sodium methylate 、 sodium hydride 、 碳酸氢钠 、 mercury dichloride 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 丙酮 为溶剂， 25.0~80.0 ℃ 、101.33 kPa 条件下， 反应 111.5h， 生成 1,5-dideoxy-1,5-imino-L-galactitol
  参考文献：
  名称：

  Paulsen, Hans; Matzke, Michael; Orthen, Bruno, Liebigs Annalen der Chemie, 1990, # 10, p. 953 - 963

  摘要：

  DOI：

文献信息

• Looking-Glass Synergistic Pharmacological Chaperones: DGJ and L-DGJ from the Enantiomers of Tagatose
  作者：Sarah F. Jenkinson、George W. J. Fleet、Robert J. Nash、Yuriko Koike、Isao Adachi、Akihide Yoshihara、Kenji Morimoto、Ken Izumori、Atsushi Kato

  DOI：10.1021/ol201552q

  日期：2011.8.5

  The enantiomers of tagatose are converted to L-DGJ [a noncompetitive inhibitor of human lysosome alpha-galactosidase A (alpha-Gal A), K-i 38.5 mu M] and DGJ [a competitive inhibitor of alpha-Gal A, K-i 15.1 nM] in 66% yield. L-DGJ and DGJ provide the first examples of pharmacological chaperones that (a) are enantiomeric iminosugars and (b) have synergistic activity with implications for the treatment of lysosomal storage disorders and other protein deficiencies.
• PAULSEN, HANS;MATZKE, MICHAEL;ORTHEN, BRUNO;NUCK, ROLF;REUTTER, WERNER, LIEBIGS ANN. CHEM.,(1990) N0, C. 953-963
  作者：PAULSEN, HANS、MATZKE, MICHAEL、ORTHEN, BRUNO、NUCK, ROLF、REUTTER, WERNER

  DOI：——

  日期：——
• 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.