(6R,7R,8S)-7,8-Bis-benzyloxy-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridin-6-ol | 266688-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: (6R,7R,8S)-7,8-Bis-benzyloxy-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridin-6-ol
• 英文别名: (6R,7R,8S)-7,8-bis(phenylmethoxy)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-ol
• CAS: 266688-23-7
• 化学式: C₂₁H₂₂N₂O₃
• 分子量: 350.417
• InChiKey: UNJHTFGJBAJIKS-VAMGGRTRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  56.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (6R,7R,8S)-7,8-Bis-benzyloxy-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridin-6-ol 在 palladium dihydroxide 氢气 、 溶剂黄146 作用下， 20.0 ℃ 、100.0 kPa 条件下， 反应 15.0h， 以69%的产率得到(6R,7R,8S)-5,6,7,8-Tetrahydro-imidazo[1,2-a]pyridine-6,7,8-triol
  参考文献：
  名称：

  Synthesis of Imidazolo-Piperidinopentoses as Nagstatine Analogues

  摘要：

  The syntheses of the four imidazolo-piperidino-pentoses 3-6, which belong to the D-series, and of their L-enantiomers, ent-3 to ent-6, are reported. Ascorbic acid and isoascorbic acid were converted over several steps into the L-threo/L-erythro- and the D-erythro/D-threo-configured aldotetroses, respectively, which are the key building blocks for the eight target imidazolo-pentoses cited above. Nucleophilic addition of a metallated imidazole to any one of these four aldotetroses gave the corresponding two diastereomeric adducts, intramolecular cyclisation of which provided the expected bicyclic target molecules, with some protection and deprotection steps being unavoidable prerequisites. The structures and configurations of all eight piperidinoses in Scheme 1 were determined unambiguously, by a combination of H-1/C-13 NMR spectroscopy, circular dichroism (CD) and MD values, in conjunction with single-crystal X-ray diffraction analyses of the L-arabino and D-lyxo azasugars ent-3 and 6. Although lacking the hydroxymethylene group in the C(5) position, the overall structure of these eight stereomers strongly resembles that of the natural product nagstatine (1), a potent inhibitor of N-acetyl-beta -D-glucosaminidase. As a matter of fact, after examination of the inhibitory properties of these imidazolo-piperidinoses against six commonly encountered glycosidases, we observe that the L-arabino imidazolo-sugar ent-3 is a potent inhibitor in this series, with K-i = 1 muM both with a beta -glucosidase and with a beta -galactosidase. The D-ribo and D-xylo stereomers 4 and 5 proved to be inhibitors of a beta -glucosidase of similar magnitude (4: K-i = 20 muM; 5: K-i = 17 muM), the other stereomers being either modest to poor inhibitors, or showing no inhibition at all.

  DOI：

  10.1002/1099-0690(200111)2001:21<4111::aid-ejoc4111>3.0.co;2-7
• 作为产物：
  描述：

  ethyl (R)-2-(benzyloxy)-2-[(4'R)-2',2'-dimethyl-1',3'-dioxolan-4'-yl]acetate 在 4-二甲氨基吡啶 、 正丁基锂 、 Dowex(R) (50WX₈) 、 水 、 四丁基碘化铵 、 sodium hydride 、 二异丁基氢化铝 、 三乙胺 、 对甲苯磺酰氯 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 53.25h， 生成 (6R,7R,8S)-7,8-Bis-benzyloxy-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridin-6-ol
  参考文献：
  名称：

  Synthesis of Imidazolo-Piperidinopentoses as Nagstatine Analogues

  摘要：

  The syntheses of the four imidazolo-piperidino-pentoses 3-6, which belong to the D-series, and of their L-enantiomers, ent-3 to ent-6, are reported. Ascorbic acid and isoascorbic acid were converted over several steps into the L-threo/L-erythro- and the D-erythro/D-threo-configured aldotetroses, respectively, which are the key building blocks for the eight target imidazolo-pentoses cited above. Nucleophilic addition of a metallated imidazole to any one of these four aldotetroses gave the corresponding two diastereomeric adducts, intramolecular cyclisation of which provided the expected bicyclic target molecules, with some protection and deprotection steps being unavoidable prerequisites. The structures and configurations of all eight piperidinoses in Scheme 1 were determined unambiguously, by a combination of H-1/C-13 NMR spectroscopy, circular dichroism (CD) and MD values, in conjunction with single-crystal X-ray diffraction analyses of the L-arabino and D-lyxo azasugars ent-3 and 6. Although lacking the hydroxymethylene group in the C(5) position, the overall structure of these eight stereomers strongly resembles that of the natural product nagstatine (1), a potent inhibitor of N-acetyl-beta -D-glucosaminidase. As a matter of fact, after examination of the inhibitory properties of these imidazolo-piperidinoses against six commonly encountered glycosidases, we observe that the L-arabino imidazolo-sugar ent-3 is a potent inhibitor in this series, with K-i = 1 muM both with a beta -glucosidase and with a beta -galactosidase. The D-ribo and D-xylo stereomers 4 and 5 proved to be inhibitors of a beta -glucosidase of similar magnitude (4: K-i = 20 muM; 5: K-i = 17 muM), the other stereomers being either modest to poor inhibitors, or showing no inhibition at all.

  DOI：

  10.1002/1099-0690(200111)2001:21<4111::aid-ejoc4111>3.0.co;2-7

文献信息

• Synthesis of Imidazolo-Piperidinopentoses as Nagstatine Analogues
  作者：François Gessier、Théophile Tschamber、Céline Tarnus、Markus Neuburger、Walter Huber、Jacques Streith

  DOI：10.1002/1099-0690(200111)2001:21<4111::aid-ejoc4111>3.0.co;2-7

  日期：2001.11

  The syntheses of the four imidazolo-piperidino-pentoses 3-6, which belong to the D-series, and of their L-enantiomers, ent-3 to ent-6, are reported. Ascorbic acid and isoascorbic acid were converted over several steps into the L-threo/L-erythro- and the D-erythro/D-threo-configured aldotetroses, respectively, which are the key building blocks for the eight target imidazolo-pentoses cited above. Nucleophilic addition of a metallated imidazole to any one of these four aldotetroses gave the corresponding two diastereomeric adducts, intramolecular cyclisation of which provided the expected bicyclic target molecules, with some protection and deprotection steps being unavoidable prerequisites. The structures and configurations of all eight piperidinoses in Scheme 1 were determined unambiguously, by a combination of H-1/C-13 NMR spectroscopy, circular dichroism (CD) and MD values, in conjunction with single-crystal X-ray diffraction analyses of the L-arabino and D-lyxo azasugars ent-3 and 6. Although lacking the hydroxymethylene group in the C(5) position, the overall structure of these eight stereomers strongly resembles that of the natural product nagstatine (1), a potent inhibitor of N-acetyl-beta -D-glucosaminidase. As a matter of fact, after examination of the inhibitory properties of these imidazolo-piperidinoses against six commonly encountered glycosidases, we observe that the L-arabino imidazolo-sugar ent-3 is a potent inhibitor in this series, with K-i = 1 muM both with a beta -glucosidase and with a beta -galactosidase. The D-ribo and D-xylo stereomers 4 and 5 proved to be inhibitors of a beta -glucosidase of similar magnitude (4: K-i = 20 muM; 5: K-i = 17 muM), the other stereomers being either modest to poor inhibitors, or showing no inhibition at all.