3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyranoside[1,2-d]-2-hexadecylsulfanyl-1,3-oxazoline | 1384841-03-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子
• 英文名称: 3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyranoside[1,2-d]-2-hexadecylsulfanyl-1,3-oxazoline
• 英文别名: [(3aS,5R,6R,7S,7aR)-6,7-diacetyloxy-2-hexadecylsulfanyl-5,6,7,7a-tetrahydro-3aH-pyrano[2,3-d][1,3]oxazol-5-yl]methyl acetate
• CAS: 1384841-03-5
• 化学式: C₂₉H₄₉NO₈S
• 分子量: 571.776
• InChiKey: IXOOTTRJZODJSA-DFLSAPQXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  39
• 可旋转键数：
  23
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  135
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyranoside[1,2-d]-2-hexadecylsulfanyl-1,3-oxazoline 在 甲醇 、 sodium methylate 作用下， 反应 20.0h， 以92%的产率得到1,2-dideoxy-α-D-glucopyranoside[1,2-d]-2-hexadecylsulfanyl-1,3-oxazoline
  参考文献：
  名称：

  Conformationally-Locked N-Glycosides with Selective β-Glucosidase Inhibitory Activity: Identification of a New Non-Iminosugar-Type Pharmacological Chaperone for Gaucher Disease

  摘要：

  A series of conformationally locked N-glycosides having a cis-1,2-fused pyranose-1,3-oxazoline-2-thione structure and bearing different substituents at the exocyclic sulfur has been prepared. The polyhydroxylated bicyclic system was built in only three steps by treatment of the corresponding readily available 1,2-anhydrosugar with KSCN using TiO(TFA)(2) as catalyst, followed by S-alkylation and acetyl deprotection. In vitro screening against several glycosidase enzymes showed highly specific inhibition of mammalian beta-glucosidase with a marked dependence of the potency upon the nature of the exocyclic substituent. The most potent representative, bearing an S-(omega-hydroxyhexadecyl) substituent, was further assayed as inhibitor of the human lysosomal beta-glucocerebrosidase and as pharmacological chaperone in Gaucher disease fibroblasts. Activity enhancements in N370S/N370S mutants analogous to those achieved with the reference compound ambroxol were attained with a more favorable chaperone/inhibitor balance.

  DOI：

  10.1021/jm3006178
• 作为产物：
  描述：

  1,2-anhydro-3,4,6-tri-O-aceyl-β-D-mannopyranose 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 26.0h， 生成 3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyranoside[1,2-d]-2-hexadecylsulfanyl-1,3-oxazoline
  参考文献：
  名称：

  Conformationally-Locked N-Glycosides with Selective β-Glucosidase Inhibitory Activity: Identification of a New Non-Iminosugar-Type Pharmacological Chaperone for Gaucher Disease

  摘要：

  A series of conformationally locked N-glycosides having a cis-1,2-fused pyranose-1,3-oxazoline-2-thione structure and bearing different substituents at the exocyclic sulfur has been prepared. The polyhydroxylated bicyclic system was built in only three steps by treatment of the corresponding readily available 1,2-anhydrosugar with KSCN using TiO(TFA)(2) as catalyst, followed by S-alkylation and acetyl deprotection. In vitro screening against several glycosidase enzymes showed highly specific inhibition of mammalian beta-glucosidase with a marked dependence of the potency upon the nature of the exocyclic substituent. The most potent representative, bearing an S-(omega-hydroxyhexadecyl) substituent, was further assayed as inhibitor of the human lysosomal beta-glucocerebrosidase and as pharmacological chaperone in Gaucher disease fibroblasts. Activity enhancements in N370S/N370S mutants analogous to those achieved with the reference compound ambroxol were attained with a more favorable chaperone/inhibitor balance.

  DOI：

  10.1021/jm3006178