(1S,2R,8R,8aS)-2,8-bis(benzyloxy)-1-hydroxyhexahydroindolizin-5(1H)-one | 1393529-11-7

• 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)-2,8-bis(benzyloxy)-1-hydroxyhexahydroindolizin-5(1H)-one
• 英文别名: (1S,2R,8R,8aS)-1-hydroxy-2,8-bis(phenylmethoxy)-2,3,6,7,8,8a-hexahydro-1H-indolizin-5-one
• CAS: 1393529-11-7
• 化学式: C₂₂H₂₅NO₄
• 分子量: 367.445
• InChiKey: ICZMSIDRYFCXPO-UGESXGAOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,2R,8R,8aS)-2,8-bis(benzyloxy)-1-hydroxyhexahydroindolizin-5(1H)-one 在 吡啶 、 20 % Pd(OH)2/C 、 氢气 、 四丁基碘化铵 、 溶剂黄146 、 2,4,6-三叔丁基嘧啶 作用下， 以 甲醇 、 乙酸乙酯 、 甲苯 为溶剂， 50.0~55.0 ℃ 、482.64 kPa 条件下， 反应 132.0h， 生成 (1S,2R,8R,8aR)-2,8-bis(acetoxy)-1-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyloxy)-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：

  溴甲苯 在 四丁基碘化铵 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 63.5h， 生成 (1S,2R,8R,8aS)-2,8-bis(benzyloxy)-1-hydroxyhexahydroindolizin-5(1H)-one 、 (1S,2R,8R,8aR)-1,2,8-tris(benzyloxy)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

文献信息

• Fleetamine (3-O-α-d-glucopyranosyl-swainsonine): the synthesis of a hypothetical inhibitor of endo-α-mannosidase
  作者：Tim Quach、Sammi Tsegay、Andrew J. Thompson、Nikolay V. Kukushkin、Dominic S. Alonzi、Terry D. Butters、Gideon J. Davies、Spencer J. Williams

  DOI：10.1016/j.tetasy.2012.06.011

  日期：2012.7

  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.