3,6-di-O-benzyl-N-butyl-2-O-butyl-1,5-dideoxy-1,5-imino-D-glucitol | 858675-43-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,6-di-O-benzyl-N-butyl-2-O-butyl-1,5-dideoxy-1,5-imino-D-glucitol
• 英文别名: (2R,3R,4S,5S)-5-butoxy-1-butyl-4-phenylmethoxy-2-(phenylmethoxymethyl)piperidin-3-ol
• CAS: 858675-43-1
• 化学式: C₂₈H₄₁NO₄
• 分子量: 455.638
• InChiKey: APTQGCMWQNBRQJ-JUDWXZBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,6-di-O-benzyl-N-butyl-2-O-butyl-1,5-dideoxy-1,5-imino-D-glucitol 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以81%的产率得到N-butyl-2-O-butyl-1,5-dideoxy-1,5-imino-D-glucitol
  参考文献：
  名称：

  Design and synthesis of iminosugar-based inhibitors of glucosylceramide synthase: the search for new therapeutic agents against Gaucher disease

  摘要：

  A series Of iminosugars bearing two or three alkyl chains ('iminoglycolipids') were designed as ceramide mimics and analogues of N-butyl 1-deoxynojirimycin (N-Bu DNJ, Zavesca(R)). This orally active iminosugar inhibits the biosynthesis of glucosylceramides. which accumulate pathologically in macrophages of patients with Gaucher disease (substrate reduction therapy, SRT). Molecular modeling and kinetic experiments have suggested that N-Bu DNJ is a competitive inhibitor that mimics the ceramide acceptor but not the donor substrate (UDP-glucose) in the glucosylceramide synthase-catalyzed process. Kinetic measurements were made with the glucosyltransferase to assess the selectivity of the new iminoglycolipids with respect to the length (C-4 or C-8) and the position of the second alkyl chain (C-1, O-2 and/or O-4). This structure-activity relationship study showed that the addition of a second alkyl chain, to obtain better ceramide mimics, led to less potent inhibitors. Moreover, the synthase active site did not discriminate inhibitors differing by the position of the second alkyl chain (C-1, O-2 or O-4). Best inhibition Was found for 1,5-dideoxy-1.5-iimino-N-octyl-4-O-octyl-D-glucitol (IC50 134 mu M). (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2005.03.015
• 作为产物：
  描述：

  1,4-di-O-benzyl-2,3-O-isopropylidene-α-L-sorbofuranose 在 四丁基碘化铵 、 sodium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 120.0h， 生成 3,6-di-O-benzyl-N-butyl-2-O-butyl-1,5-dideoxy-1,5-imino-D-glucitol
  参考文献：
  名称：

  Design and synthesis of iminosugar-based inhibitors of glucosylceramide synthase: the search for new therapeutic agents against Gaucher disease

  摘要：

  A series Of iminosugars bearing two or three alkyl chains ('iminoglycolipids') were designed as ceramide mimics and analogues of N-butyl 1-deoxynojirimycin (N-Bu DNJ, Zavesca(R)). This orally active iminosugar inhibits the biosynthesis of glucosylceramides. which accumulate pathologically in macrophages of patients with Gaucher disease (substrate reduction therapy, SRT). Molecular modeling and kinetic experiments have suggested that N-Bu DNJ is a competitive inhibitor that mimics the ceramide acceptor but not the donor substrate (UDP-glucose) in the glucosylceramide synthase-catalyzed process. Kinetic measurements were made with the glucosyltransferase to assess the selectivity of the new iminoglycolipids with respect to the length (C-4 or C-8) and the position of the second alkyl chain (C-1, O-2 and/or O-4). This structure-activity relationship study showed that the addition of a second alkyl chain, to obtain better ceramide mimics, led to less potent inhibitors. Moreover, the synthase active site did not discriminate inhibitors differing by the position of the second alkyl chain (C-1, O-2 or O-4). Best inhibition Was found for 1,5-dideoxy-1.5-iimino-N-octyl-4-O-octyl-D-glucitol (IC50 134 mu M). (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2005.03.015

文献信息

• A stereodivergent approach to 1-deoxynojirimycin, 1-deoxygalactonojirimycin and 1-deoxymannojirimycin derivatives
  作者：Charlotte Boucheron、Philippe Compain、Olivier R. Martin

  DOI：10.1016/j.tetlet.2006.02.157

  日期：2006.5

  A stereodivergent synthesis of N-alkylated 1-deoxygalactoncjirimycin and 1-deoxymannojirimycin derivatives has been achieved from a protected 1-deoxynojirimycin intermediate having two free OH groups tactically positioned at C-2 and C-4. The inversion of configuration of the secondary alcohols was performed by way of a Swern oxidation followed by a highly diastereoselective reduction using NaBH4 or L-Selectride. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis of 4-O-glycosylated 1-deoxynojirimycin derivatives as disaccharide mimics-based inhibitors of human β-glucocerebrosidase
  作者：Charlotte Boucheron、Sylvestre Toumieux、Philippe Compain、Olivier R. Martin、Kyoko Ikeda、Naoki Asano

  DOI：10.1016/j.carres.2007.03.015

  日期：2007.9

  Examples of a new type of inhibitor of human -glucocerebrosidase based on imino-disaccharides as glycosylceramide mimetics have been synthesized by way of the glycosylation of 1-deoxynojirimycin derivatives with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide. (c) 2007 Elsevier Ltd. All rights reserved.