(1S,2R,8R,8aR)-2,8-bis(hydroxy)-1-(α-D-glucopyranosyloxy)-octahydroindolizine hydrochloride | 1393529-09-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S,2R,8R,8aR)-2,8-bis(hydroxy)-1-(α-D-glucopyranosyloxy)-octahydroindolizine hydrochloride
• 英文别名: 3-O-α-D-glucopyranosyl-swainsonine hydrochloride；fleetamine hydrochloride；(2S,3R,4S,5S,6R)-2-[[(1S,2R,8R,8aR)-2,8-dihydroxy-1,2,3,5,6,7,8,8a-octahydroindolizin-1-yl]oxy]-6-(hydroxymethyl)oxane-3,4,5-triol;hydrochloride
• CAS: 1393529-09-3
• 化学式: C₁₄H₂₅NO₈*ClH
• 分子量: 371.815
• InChiKey: PMKDDCXBPXFNKX-ONFXSTFNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.21
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  143
• 氢给体数：
  7
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1,6-二-O-乙酰基-2,3,4-三-O-苄基-beta-D-吡喃葡萄糖 在 吡啶 、 碘代三甲硅烷 、 dimethyl sulfide borane 、 20 % Pd(OH)2/C 、 氢气 、 sodium methylate 、 四丁基碘化铵 、 溶剂黄146 、 2,4,6-三叔丁基嘧啶 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， 55.0 ℃ 、482.64 kPa 条件下， 反应 138.0h， 生成 (1S,2R,8R,8aR)-2,8-bis(hydroxy)-1-(α-D-glucopyranosyloxy)-octahydroindolizine hydrochloride
  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.