(5R,6R,7R,8S)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydrotriazolo[4,3-a]pyridin-8-ol | 182074-17-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡啶类
• 英文名称: (5R,6R,7R,8S)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydrotriazolo[4,3-a]pyridin-8-ol
• 英文别名: (5R,6R,7R,8R)-6,7-bis(phenylmethoxy)-5-(phenylmethoxymethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridin-8-ol
• CAS: 182074-17-5
• 化学式: C₂₈H₂₉N₃O₄
• 分子量: 471.556
• InChiKey: MJGNIQHWTZOHSP-HVWQDESWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (5R,6R,7R,8S)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydrotriazolo[4,3-a]pyridin-8-ol 在 palladium on activated charcoal 吡啶 、 sodium azide 、 氢气 作用下， 以 甲醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 70.0 ℃ 、600.0 kPa 条件下， 反应 26.5h， 生成 (5R,6R,7S,8S)-8-amino-5,6,7,8-tetrahydro-5-(hydroxymethyl)[1,2,4]triazolo[4,3-a]pyridine-6,7-diol
  参考文献：
  名称：

  摘要：

  The inhibition of the beta-glucosidases from sweet almonds and Caldocellum saccharolyticum at varying pH values by the glucosamine-related inhibitors 1-7 has been compared to the inhibition by the known glucose analogues 8-14. The amino derivatives 3, 4, 6, and 7 were prepared in one step from the known 15-18 (Scheme I), and the amino-1,2,3-triazole 5 by a variant of the synthesis leading to the glucose analogue 12 (Scheme 2). The key step Tor the preparation of the aminoimidazole 1 and of the amino-1,2,4-triazole 2 is the regioselective cleavage of the benzyloxy group at C(2) of the gluconolactam 35 and the mannonolactam 57 respectively, by BCl3 and B4NBr (Schemes 3 and 4, resp.). The pH optimum for the inhibition by the amines is lower than their pK(HA) values, evidencing that they are bound as ammonium salts and that H-bonding between C(2)-NH3+ and the cat. base B- contributes more strongly to binding than any possible H-bond to the NH2-C(2) group. The influence of the ammonium group on the inhibitory strength correlates with the basicity of the 'glycosidic heteroatom'. The strongest increase of the inhibitory strength is observed for the amines lacking a 'glycosidic heteroatom' (Delta Delta G(OH-->NH3+)=-1.5 to -2.9 kcal/mol). The increase is less; derivatives 3-4, which possess a weakly basic 'glycosidic heteroatom' pronounced for the amino derivatives 3-4, which possess a weakly basic 'glycosidic heteroatom' (Delta Delta G(OH --> NH3+) = - 0.6 to - 1.1 kcal/mol); the amino compounds 1 and 2, which possess a strongly basic 'glycosidic heteroatom', are weaker inhibitors than the corresponding hydroxy compounds, as expressed by Delta Delta G(OH-->NH3+) between +4.3 and +4.7 kcal/mol for the amino-imidazole 1, and between +2.3 and 2.8 kcal/mol for the amino-1,2,4-triazole 2, denoting the dominant detrimental influence of a C(2) -NH3+ group on the H-bond acceptor properties of a sufficiently basic 'glycosidic heteroatom'.

  DOI：

  10.1002/(sici)1522-2675(20000315)83:3<513::aid-hlca513>3.0.co;2-1
• 作为产物：
  描述：

  2-O-acetyl-5-amino-3,4,6-tri-O-benzyl-5-deoxy-D-mannonothiolactam 在 mercury(II) diacetate 、 氨 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.5h， 生成 (5R,6R,7R,8S)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydrotriazolo[4,3-a]pyridin-8-ol
  参考文献：
  名称：

  摘要：

  The inhibition of the beta-glucosidases from sweet almonds and Caldocellum saccharolyticum at varying pH values by the glucosamine-related inhibitors 1-7 has been compared to the inhibition by the known glucose analogues 8-14. The amino derivatives 3, 4, 6, and 7 were prepared in one step from the known 15-18 (Scheme I), and the amino-1,2,3-triazole 5 by a variant of the synthesis leading to the glucose analogue 12 (Scheme 2). The key step Tor the preparation of the aminoimidazole 1 and of the amino-1,2,4-triazole 2 is the regioselective cleavage of the benzyloxy group at C(2) of the gluconolactam 35 and the mannonolactam 57 respectively, by BCl3 and B4NBr (Schemes 3 and 4, resp.). The pH optimum for the inhibition by the amines is lower than their pK(HA) values, evidencing that they are bound as ammonium salts and that H-bonding between C(2)-NH3+ and the cat. base B- contributes more strongly to binding than any possible H-bond to the NH2-C(2) group. The influence of the ammonium group on the inhibitory strength correlates with the basicity of the 'glycosidic heteroatom'. The strongest increase of the inhibitory strength is observed for the amines lacking a 'glycosidic heteroatom' (Delta Delta G(OH-->NH3+)=-1.5 to -2.9 kcal/mol). The increase is less; derivatives 3-4, which possess a weakly basic 'glycosidic heteroatom' pronounced for the amino derivatives 3-4, which possess a weakly basic 'glycosidic heteroatom' (Delta Delta G(OH --> NH3+) = - 0.6 to - 1.1 kcal/mol); the amino compounds 1 and 2, which possess a strongly basic 'glycosidic heteroatom', are weaker inhibitors than the corresponding hydroxy compounds, as expressed by Delta Delta G(OH-->NH3+) between +4.3 and +4.7 kcal/mol for the amino-imidazole 1, and between +2.3 and 2.8 kcal/mol for the amino-1,2,4-triazole 2, denoting the dominant detrimental influence of a C(2) -NH3+ group on the H-bond acceptor properties of a sufficiently basic 'glycosidic heteroatom'.

  DOI：

  10.1002/(sici)1522-2675(20000315)83:3<513::aid-hlca513>3.0.co;2-1

文献信息

• Synthesis and Glycosidase Inhibitory Activities of Nagstatin Triazole Analogs.
  作者：KUNIAKI TATSUTA、YUICHI IKEDA、SHOZO MIURA

  DOI：10.7164/antibiotics.49.836

  日期：——
• ——
  作者：Narendra Panday、Muthuppalaniappan Meyyappan、Andrea Vasella

  DOI：10.1002/(sici)1522-2675(20000315)83:3<513::aid-hlca513>3.0.co;2-1

  日期：2000.3.15

  The inhibition of the beta-glucosidases from sweet almonds and Caldocellum saccharolyticum at varying pH values by the glucosamine-related inhibitors 1-7 has been compared to the inhibition by the known glucose analogues 8-14. The amino derivatives 3, 4, 6, and 7 were prepared in one step from the known 15-18 (Scheme I), and the amino-1,2,3-triazole 5 by a variant of the synthesis leading to the glucose analogue 12 (Scheme 2). The key step Tor the preparation of the aminoimidazole 1 and of the amino-1,2,4-triazole 2 is the regioselective cleavage of the benzyloxy group at C(2) of the gluconolactam 35 and the mannonolactam 57 respectively, by BCl3 and B4NBr (Schemes 3 and 4, resp.). The pH optimum for the inhibition by the amines is lower than their pK(HA) values, evidencing that they are bound as ammonium salts and that H-bonding between C(2)-NH3+ and the cat. base B- contributes more strongly to binding than any possible H-bond to the NH2-C(2) group. The influence of the ammonium group on the inhibitory strength correlates with the basicity of the 'glycosidic heteroatom'. The strongest increase of the inhibitory strength is observed for the amines lacking a 'glycosidic heteroatom' (Delta Delta G(OH-->NH3+)=-1.5 to -2.9 kcal/mol). The increase is less; derivatives 3-4, which possess a weakly basic 'glycosidic heteroatom' pronounced for the amino derivatives 3-4, which possess a weakly basic 'glycosidic heteroatom' (Delta Delta G(OH --> NH3+) = - 0.6 to - 1.1 kcal/mol); the amino compounds 1 and 2, which possess a strongly basic 'glycosidic heteroatom', are weaker inhibitors than the corresponding hydroxy compounds, as expressed by Delta Delta G(OH-->NH3+) between +4.3 and +4.7 kcal/mol for the amino-imidazole 1, and between +2.3 and 2.8 kcal/mol for the amino-1,2,4-triazole 2, denoting the dominant detrimental influence of a C(2) -NH3+ group on the H-bond acceptor properties of a sufficiently basic 'glycosidic heteroatom'.