(2R,3S,4R)-3,4-Bis-benzyloxy-4-(1H-imidazol-2-yl)-butane-1,2-diol | 399508-55-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R,3S,4R)-3,4-Bis-benzyloxy-4-(1H-imidazol-2-yl)-butane-1,2-diol
• 英文别名: (2R,3S,4R)-4-(1H-imidazol-2-yl)-3,4-bis(phenylmethoxy)butane-1,2-diol
• CAS: 399508-55-5
• 化学式: C₂₁H₂₄N₂O₄
• 分子量: 368.433
• InChiKey: WSICZYBZVHHJSB-AABGKKOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  87.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3S,4R)-3,4-Bis-benzyloxy-4-(1H-imidazol-2-yl)-butane-1,2-diol 在 二正丁基氧化锡 、 三乙胺 、 对甲苯磺酰氯 、 sodium hydroxide 、 水 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 24.0h， 以90%的产率得到(6R,7S,8R)-7,8-dibenzyloxy-6-hydroxy-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine
  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：

  (1R,2R)-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenylmethoxy-1-(1-tritylimidazol-2-yl)ethanol 在 盐酸 、 水 、 四丁基碘化铵 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 (2R,3S,4R)-3,4-Bis-benzyloxy-4-(1H-imidazol-2-yl)-butane-1,2-diol
  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

• Carbohydrate transition state mimics: synthesis of imidazolo-Pyrrolidinoses as potential nectrisine surrogates
  作者：Théophile Tschamber、François Gessier、Estelle Dubost、Jeffery Newsome、Céline Tarnus、Josiane Kohler、Markus Neuburger、Jacques Streith

  DOI：10.1016/s0968-0896(03)00402-4

  日期：2003.8

  The syntheses of four glyco-imidazoles, which are pentose-derivatives belonging to the D-series, as well as the syntheses of their (L)-enantiomers, are reported. Starting from the known linear xylo, lyxo, arabino, and ribo imidazolo-pentoses in both the Land the D-series, intramolecular Walden inversion led to the corresponding arabino, ribo, xylo, and lyxo pyrrolidinopentoses in the (D)- and the (L)-series, respectively, protection and deprotection steps being unavoidable prerequisites. The structures and configurations of all eight pyrrolidinopentoses were determined unambiguously, by a combination of H-1/C-13 NMR spectroscopy, circular dichroism and [alpha](D) values, in conjunction with single-crystal X-ray diffraction analysis of the (L)-xylo stereoisomer. Examination of the inhibitory properties of these imidazolo-pyrrolidinoses against six commonly encountered glycosidases led to the conclusion that by and large the (L)-stereoisomers are inactive, whereas three out the four (D)-stereoisomers proved to be poor to moderate inhibitors. It appears therefore that the most basic N(1) atom is not located in an optimal topology to be protonated easily inside the enzyme's active site. (C) 2003 Elsevier Ltd. All rights reserved.
• 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.