2-O-acetyl-5-amino-3,4,6-tri-O-benzyl-5-deoxy-D-gluconothiolactam | 272124-00-2

• 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: 2-O-acetyl-5-amino-3,4,6-tri-O-benzyl-5-deoxy-D-gluconothiolactam
• 英文别名: [(3R,4S,5R,6R)-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)-2-sulfanylidenepiperidin-3-yl] acetate
• CAS: 272124-00-2
• 化学式: C₂₉H₃₁NO₅S
• 分子量: 505.635
• InChiKey: SOLQITGDBOOYQS-ZZXHUEHTSA-N

物化性质

• 沸点：
  609.5±65.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  98.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-O-acetyl-5-amino-3,4,6-tri-O-benzyl-5-deoxy-D-gluconothiolactam 在 mercury(II) diacetate 、 水 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 13.0h， 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：

  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-gluconolactam 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以92%的产率得到2-O-acetyl-5-amino-3,4,6-tri-O-benzyl-5-deoxy-D-gluconothiolactam
  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 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