(1S,2R,8R,8aS)-8-benzyloxy-1,2-dihydroxyhexahydroindolizin-5(1H)-one | 1393529-10-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚里西啶
• 英文名称: (1S,2R,8R,8aS)-8-benzyloxy-1,2-dihydroxyhexahydroindolizin-5(1H)-one
• CAS: 1393529-10-6
• 化学式: C₁₅H₁₉NO₄
• 分子量: 277.32
• InChiKey: ZWAKCEGWOJBLJU-QHSBEEBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  70.0
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (1S,2R,8R,8aS)-8-benzyloxy-1,2-dihydroxyhexahydroindolizin-5(1H)-one 在 吡啶 、 四丁基碘化铵 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 22.5h， 生成 (1S,2R,8R,8aR)-2,8-bis(benzyloxy)-1-acetoxy-hexahydroindolizin-5(1H)-one
  参考文献：
  名称：

  Fleetamine (3-O-α-d-glucopyranosyl-swainsonine): the synthesis of a hypothetical inhibitor of endo-α-mannosidase

  摘要：

  3-O-alpha-D-Glucopyranosyl-swainsonine was originally proposed(17) as a potential inhibitor of the mammalian enzyme endo-alpha-mannosidase, but its synthesis has not been reported. Herein we report the total synthesis of this enigmatic compound, utilizing a halide-ion catalysed glycosylation of a swainsonine lactam with a glucosyl iodide donor as the key step. The resulting inhibitor was evaluated as an inhibitor of human endo-alpha-mannosidase, and as a ligand for bacterial orthologs from Bacteroides thetaiotaomicron and Bacteroides xylanisolvens, including active-centre variants, although no evidence for binding or inhibition was observed. The surprising lack of binding was rationalized by using structural alignment with an endo-alpha-mannosidase inhibitor complex, which identified deleterious interactions with the swainsonine piperidine ring and an essential active site residue. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2012.06.011
• 作为产物：
  描述：

  (1S,2R,8R,8aR)-8-hydroxy-1,2-(isopropylidenedioxy)octahydroindolizin-5-one 在 四丁基碘化铵 、 sodium hydride 、 对甲苯磺酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 (1S,2R,8R,8aS)-8-benzyloxy-1,2-dihydroxyhexahydroindolizin-5(1H)-one
  参考文献：
  名称：

  Fleetamine (3-O-α-d-glucopyranosyl-swainsonine): the synthesis of a hypothetical inhibitor of endo-α-mannosidase

  摘要：

  3-O-alpha-D-Glucopyranosyl-swainsonine was originally proposed(17) as a potential inhibitor of the mammalian enzyme endo-alpha-mannosidase, but its synthesis has not been reported. Herein we report the total synthesis of this enigmatic compound, utilizing a halide-ion catalysed glycosylation of a swainsonine lactam with a glucosyl iodide donor as the key step. The resulting inhibitor was evaluated as an inhibitor of human endo-alpha-mannosidase, and as a ligand for bacterial orthologs from Bacteroides thetaiotaomicron and Bacteroides xylanisolvens, including active-centre variants, although no evidence for binding or inhibition was observed. The surprising lack of binding was rationalized by using structural alignment with an endo-alpha-mannosidase inhibitor complex, which identified deleterious interactions with the swainsonine piperidine ring and an essential active site residue. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2012.06.011