5-amino-3,4,6-tri-O-benzyl-5-deoxy-2-O-(triisopropylsilyl)-D-glucono-1,5-thiolactam | 848782-16-1

• 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-(triisopropylsilyl)-D-glucono-1,5-thiolactam
• 英文别名: (3R,4S,5R,6R)-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)-3-tri(propan-2-yl)silyloxypiperidine-2-thione
• CAS: 848782-16-1
• 化学式: C₃₆H₄₉NO₄SSi
• 分子量: 619.941
• InChiKey: YOYHWUXSJPHOIW-NDLNHBFLSA-N

物化性质

• 沸点：
  645.1±65.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.23
• 重原子数：
  43
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  81
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-amino-3,4,6-tri-O-benzyl-5-deoxy-2-O-(triisopropylsilyl)-D-glucono-1,5-thiolactam 、 氨基乙醛缩二甲醇 在 对甲苯磺酸 mercury(II) diacetate 、 水 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 以90%的产率得到(5R,6R,7S,8S)-6,7-bis(benzyloxy)-5-[(benzyloxy)methyl]-5,6,7,8-tetrahydro-8-(triisopropylsilyl)imidazo[1,2-a]pyridine
  参考文献：
  名称：

  Inhibition of O-GlcNAcase by a gluco-configured nagstatin and a PUGNAc–imidazole hybrid inhibitor

  摘要：

  合成 PUGNAcâimidazole 混合物，并通过酶动力学和 X 射线结构分析确定其作为人 O-GlcNA 酶抑制剂的特性。

  DOI：

  10.1039/b612154c
• 作为产物：
  描述：

  5-amino-3,4,6-tri-O-benzyl-5-deoxy-D-gluconolactam 在 劳森试剂 、 吡啶 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 39.5h， 生成 5-amino-3,4,6-tri-O-benzyl-5-deoxy-2-O-(triisopropylsilyl)-D-glucono-1,5-thiolactam
  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 ofN-Acetylglucosamine-Derived Nagstatin Analogues and Their Evaluation as Glycosidase Inhibitors
  作者：Miroslav Terinek、Andrea Vasella

  DOI：10.1002/hlca.200490286

  日期：2005.1

  are nanomolar inhibitors of the N-acetyl-β-glucosaminidases from Jack beans and from bovine kidney, submicromolar to micromolar inhibitors of the β-glucosidase from Caldocellum saccharolyticum, and rather weak inhibitors of the snail β-mannosidase. In all cases, the ester was a stronger inhibitor than the corresponding acid. As expected from their gluco-configuration, both imidazopyridines 14 and 15 are

  通过硫代内酰胺17或18与β-氨基酯19的缩合反应合成了那格他汀（1）的葡萄糖类似物15和甲酯14。由17得到的甲硅烷基醚20和21被甲硅烷基化为22和23。这些醇是通过缩合18和19直接得到的。在Mitsunobu下尝试用叠氮化物取代22的C（8）OH基团条件出乎意料地导致了脱氧的α-叠氮基酯24。所需的叠氮化物25是通过用叠氮磷酸二苯酯处理甘露聚糖构型的醇23而获得的。叠氮化物被转化为脱苄基的乙酰氨基酯14，该酯被水解为那格他汀类似物15。咪唑-2-乙酸盐14和15是来自Jack豆和牛肾的N-乙酰-β-氨基葡萄糖苷酶的纳摩尔抑制剂，来自于亚摩尔至微摩尔的β-葡萄糖苷酶的纳摩尔抑制剂。Caldocellum saccharolyticum和蜗牛β-甘露糖苷酶的弱抑制剂。在所有情况下，该酯都是比相应的酸更强的抑制剂。如从它们的葡萄糖构型所预期的，咪唑并吡啶14和15都是来自牛肾的β - N
• 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.
• Inhibition of O-GlcNAcase by a gluco-configured nagstatin and a PUGNAc–imidazole hybrid inhibitor
  作者：Bhagavathy Shanmugasundaram、Aleksandra W. Debowski、Rebecca J. Dennis、Gideon J. Davies、David J. Vocadlo、Andrea Vasella

  DOI：10.1039/b612154c

  日期：——

  Synthesis of a PUGNAc–imidazole hybrid and its characterization as an inhibitor of human O-GlcNAcase through enzyme kinetics and X-ray structural analysis.

  合成 PUGNAcâimidazole 混合物，并通过酶动力学和 X 射线结构分析确定其作为人 O-GlcNA 酶抑制剂的特性。