(5R,6R,7S,8S)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-ol | 162491-59-0

• 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: (5R,6R,7S,8S)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-ol
• 英文别名: (5R,6R,7R,8S)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-ol；(5R,6R,7R,8S)-6,7-bis(phenylmethoxy)-5-(phenylmethoxymethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-ol
• CAS: 162491-59-0
• 化学式: C₂₉H₃₀N₂O₄
• 分子量: 470.568
• InChiKey: BMQVWUOUTFNQKU-BIYDSLDMSA-N

物化性质

• 沸点：
  660.9±55.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  65.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (5R,6R,7S,8S)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-ol 在 sodium tetrahydroborate 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (5R,6R,7S,8R)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-ol
  参考文献：
  名称：

  Synthesis and evaluation of two mannosamine-derived lactone-type inhibitors of snail β-mannosidase

  摘要：

  The inhibition of snail beta-mannosidase by the manno-configured amino- and hydroxy-lactams and -imidazoles 7-10 was compared to the inhibition of the beta-glucosidases from Caldocellum saccharolyticum and from sweet almonds by the gluco-configured amino- and hydroxy-lactams and -imidazoles 1, 2, 5 and 6 [DeltaDeltaG(diss)(OH --> NH3+)]- Substitution in the gluco-configured 1, 3 and 5, of C(2)-OH by an ammonium group strengthens the interaction of the inhibitor with the catalytic nucleophile of retaining beta-glucosidases, and weakens the interaction with the catalytic acid. The analogous substitution in the manno-configured inhibitors 7 and 9, leading to 8 and 10, respectively, was expected to only reflect the impaired interaction of the inhibitor with the catalytic acid, as the catalytic nucleophile and the C(2) substitueut are located on opposite sides of the average ring plane.The mannonolactam 10 was synthesized from the known hydroxy-lactam 11 by O-mesylation followed by azidation and hydrogenation. Sultone 13 was formed as side product upon mesylation of 11. The imidazole 8 was obtained from 11, similarly to the synthesis of the known gluco-isomer 2, via the hydroxy-imidazoles 22 and 23; best results were obtained by protecting 11 as the triisopropylsilyl ether 29.The resulting inhibition by the imidazoles 7 and 8 was interpreted as reflecting an improved binding of the catalytic nucleophile of snail P-mannosidase with the protonated imidazolc ring of 8 and an impaired interaction with the catalytic acid, while a comparison of the inhibition by the lactams 9 and 10 is in keeping with the results that are expected if there is no significant interaction between the catalytic nucleophile of snail beta-mannosidase and the C(2)-OH group of beta-mannosides. The amino-imidazole 8 is a surprisingly strong inhibitor of the a-mannosidase from Jack beans [K-i = 1.22 muM; mixed-type (alpha = 2.3)]. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.11.068
• 作为产物：
  描述：

  (5R,6R,7S,8R)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-ol 在 三丁基膦 、 sodium methylate 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.5h， 生成 (5R,6R,7S,8S)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-ol
  参考文献：
  名称：

  总分支的那格他汀及其具有糖苷酶抑制活性的类似物的合成

  摘要：

  去支化的那格他汀及其类似物已经通过与咪唑部分的分子间和分子内亲核反应，从受保护的L-核糖基和木糖基呋喃糖合成。

  DOI：

  10.1016/0040-4039(94)02460-s

文献信息

• Syntheses and Glycosidase Inhibiting Activities of Nagstatin Analogs.
  作者：KUNIAKI TATSUTA、SHOZO MIURA、SHIGERU OHTA、HIROKI GUNJI

  DOI：10.7164/antibiotics.48.286

  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'.
• Synthesis and evaluation of two mannosamine-derived lactone-type inhibitors of snail β-mannosidase
  作者：Miroslav Terinek、Andrea Vasella

  DOI：10.1016/j.tetasy.2004.11.068

  日期：2005.1

  The inhibition of snail beta-mannosidase by the manno-configured amino- and hydroxy-lactams and -imidazoles 7-10 was compared to the inhibition of the beta-glucosidases from Caldocellum saccharolyticum and from sweet almonds by the gluco-configured amino- and hydroxy-lactams and -imidazoles 1, 2, 5 and 6 [DeltaDeltaG(diss)(OH --> NH3+)]- Substitution in the gluco-configured 1, 3 and 5, of C(2)-OH by an ammonium group strengthens the interaction of the inhibitor with the catalytic nucleophile of retaining beta-glucosidases, and weakens the interaction with the catalytic acid. The analogous substitution in the manno-configured inhibitors 7 and 9, leading to 8 and 10, respectively, was expected to only reflect the impaired interaction of the inhibitor with the catalytic acid, as the catalytic nucleophile and the C(2) substitueut are located on opposite sides of the average ring plane.The mannonolactam 10 was synthesized from the known hydroxy-lactam 11 by O-mesylation followed by azidation and hydrogenation. Sultone 13 was formed as side product upon mesylation of 11. The imidazole 8 was obtained from 11, similarly to the synthesis of the known gluco-isomer 2, via the hydroxy-imidazoles 22 and 23; best results were obtained by protecting 11 as the triisopropylsilyl ether 29.The resulting inhibition by the imidazoles 7 and 8 was interpreted as reflecting an improved binding of the catalytic nucleophile of snail P-mannosidase with the protonated imidazolc ring of 8 and an impaired interaction with the catalytic acid, while a comparison of the inhibition by the lactams 9 and 10 is in keeping with the results that are expected if there is no significant interaction between the catalytic nucleophile of snail beta-mannosidase and the C(2)-OH group of beta-mannosides. The amino-imidazole 8 is a surprisingly strong inhibitor of the a-mannosidase from Jack beans [K-i = 1.22 muM; mixed-type (alpha = 2.3)]. (C) 2004 Elsevier Ltd. All rights reserved.
• Total syntheses of de-branched nagstatin and its analogs having glycosidase inhibiting activities
  作者：Kuniaki Tatsuta、Shozo Miura、Shigeru Ohta、Hiroki Gunji

  DOI：10.1016/0040-4039(94)02460-s

  日期：1995.2

  De-branched nagstatin and its analogs have been synthesized from protected L-ribo- and xylofuranoses through the inter- and intra-molecular nucleophilic reactions with the imidazole moieties.

  去支化的那格他汀及其类似物已经通过与咪唑部分的分子间和分子内亲核反应，从受保护的L-核糖基和木糖基呋喃糖合成。