1,4-di-O-benzyl-2,3-O-isopropylidene-6-O-methanesulfonyl-α-L-sorbofuranose | 858675-40-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,4-di-O-benzyl-2,3-O-isopropylidene-6-O-methanesulfonyl-α-L-sorbofuranose
• 英文别名: [(3aS,5S,6R,6aS)-2,2-dimethyl-6-phenylmethoxy-3a-(phenylmethoxymethyl)-6,6a-dihydro-5H-furo[2,3-d][1,3]dioxol-5-yl]methyl methanesulfonate
• CAS: 858675-40-8
• 化学式: C₂₄H₃₀O₈S
• 分子量: 478.563
• InChiKey: SHWXGKZAYMKUAT-KHUIQGCPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  97.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1,4-di-O-benzyl-2,3-O-isopropylidene-6-O-methanesulfonyl-α-L-sorbofuranose 在 palladium on activated charcoal 盐酸 、 氘代甲醇 、 氢气 、 四丁基碘化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 186.0h， 生成
  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：

  甲基磺酰氯 、 1,4-di-O-benzyl-2,3-O-isopropylidene-α-L-sorbofuranose 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以94%的产率得到1,4-di-O-benzyl-2,3-O-isopropylidene-6-O-methanesulfonyl-α-L-sorbofuranose
  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

• Design and synthesis of iminosugar-based inhibitors of glucosylceramide synthase: the search for new therapeutic agents against Gaucher disease
  作者：Charlotte Boucheron、Valérie Desvergnes、Philippe Compain、Olivier R. Martin、Alan Lavi、Muckram Mackeen、Mark Wormald、Raymond Dwek、Terry D. Butters

  DOI：10.1016/j.tetasy.2005.03.015

  日期：2005.5

  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.