5-amino-3,4,6-tri-O-benzyl-5-deoxy-2-O-(trifluoromethanesulfonyl)-D-mannono-1,5-lactam | 848782-06-9

• 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: 5-amino-3,4,6-tri-O-benzyl-5-deoxy-2-O-(trifluoromethanesulfonyl)-D-mannono-1,5-lactam
• 英文别名: [(3S,4S,5R,6R)-2-oxo-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)piperidin-3-yl] trifluoromethanesulfonate
• CAS: 848782-06-9
• 化学式: C₂₈H₂₈F₃NO₇S
• 分子量: 579.594
• InChiKey: SZCDQMTWKVPCII-XPGKHFPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5-amino-3,4,6-tri-O-benzyl-5-deoxy-2-O-(trifluoromethanesulfonyl)-D-mannono-1,5-lactam 在 劳森试剂 、 吡啶 、 sodium tetrahydroborate 、 sodium azide 、 mercury(II) diacetate 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 59.0h， 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：

  5-amino-3,4,6-tri-O-benzyl-5-deoxy-D-gluconolactam 在 吡啶 、 sodium azide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 5-amino-3,4,6-tri-O-benzyl-5-deoxy-2-O-(trifluoromethanesulfonyl)-D-mannono-1,5-lactam
  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

文献信息

• 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.