(2S,3S,4S,5S)-1-hydroxy-2-(benzyloxymethyl)-3,4-bis(benzyloxy)-5-(3,3-dimethoxypropyl)pyrrolidine | 1231217-52-9

• 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: (2S,3S,4S,5S)-1-hydroxy-2-(benzyloxymethyl)-3,4-bis(benzyloxy)-5-(3,3-dimethoxypropyl)pyrrolidine
• 英文别名: (2S,3S,4S,5S)-1-hydroxyl-3,4-bis-(benzyloxy)-2-((benzyloxy)methyl)-5-(3,3-dimethoxypropyl)pyrrolidine；(2S,3S,4S,5S)-2-(3,3-dimethoxypropyl)-1-hydroxy-3,4-bis(phenylmethoxy)-5-(phenylmethoxymethyl)pyrrolidine
• CAS: 1231217-52-9
• 化学式: C₃₁H₃₉NO₆
• 分子量: 521.654
• InChiKey: YAZLTIHPTDGERN-QMMMHVTISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  38
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,3S,4S,5S)-1-hydroxy-2-(benzyloxymethyl)-3,4-bis(benzyloxy)-5-(3,3-dimethoxypropyl)pyrrolidine 在 盐酸 、 manganese(IV) oxide 、 samarium diiodide 、 palladium 10% on activated carbon 、 氢气 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 30.17h， 生成 2(R)-hydroxylabystegine
  参考文献：
  名称：

  Design and Synthesis of Labystegines, Hybrid Iminosugars from LAB and Calystegine, as Inhibitors of Intestinal α-Glucosidases: Binding Conformation and Interaction for ntSI

  摘要：

  This paper identifies the required configuration and orientation of alpha-glucosidase inhibitors, miglitol, alpha-1-C-butyl-DNJ, and alpha-1-C-butyl-LAB for binding to ntSI (isomaltase). Molecular dynamics (MD) calculations suggested that the flexibility around the keyhole of ntSI is lower than that of ctSI (sucrase). Furthermore, a molecular-docking study revealed that a specific binding orientation with a CH-pi interaction (Trp370 and Phe648) is a requirement for achieving a strong affinity with ntSI. On the basis of these results, a new class of nortropane-type iminosugars, labystegines, hybrid iminosugars of LAB and calystegine, have been designed and synthesized efficiently from sugar-derived cyclic nitrones with intramolecular 1,3-dipolar cycloaddition or samarium iodide catalyzed reductive coupling reaction as the key step. Biological evaluation showed that our newly designed 3(S)-hydroxy labystegine (6a) inherited the selectivity against intestinal alpha-glucosidases from LAB, and its inhibition potency was 10 times better than that of miglitol. Labystegine, therefore, represents a promising new class of nortropane-type iminosugar for improving postprandial hyperglycemia.

  DOI：

  10.1021/acs.joc.5b00342
• 作为产物：
  描述：

  (3S,4S,5S)-3,4-dibenzyloxy-5-benzyloxymethyl-1-pyrroline-N-oxide 、 1-溴-3,3-二甲氧基丙烷 在 magnesium 作用下， 以 四氢呋喃 为溶剂， 以92%的产率得到(2S,3S,4S,5S)-1-hydroxy-2-(benzyloxymethyl)-3,4-bis(benzyloxy)-5-(3,3-dimethoxypropyl)pyrrolidine
  参考文献：
  名称：

  Exploratory Studies en Route to 5-Alkyl-Hyacinthacines: Synthesis of 5-epi-(-)-Hyacinthacine A3 and (-)-Hyacinthacine A3

  摘要：

  从d-木糖衍生的多羟基环状硝酮出发，成功合成了5-epi-(-)-风信子素A3和(-)-风信子素A3。我们的合成策略可能普遍且灵活，适用于合成5-烷基-风信子素两种异构体。

  DOI：

  10.1055/s-0029-1219540

文献信息

• Exploratory Studies en Route to 5-Alkyl-Hyacinthacines: Synthesis of 5-epi-(-)-Hyacinthacine A3 and (-)-Hyacinthacine A3
  作者：Chu-Yi Yu、Xiang-Guo Hu、Yue-Mei Jia、Junfeng Xiang

  DOI：10.1055/s-0029-1219540

  日期：2010.4

  Synthesis of 5-epi-(-)-hyacinthacine A3 and (-)-hyacinthacine A3 has been achieved from the d-xylose-derived polyhydroxylated cyclic nitrone. Our synthetic strategy is potentially general and flexible for the synthesis of both epimers of 5-alkyl-­hyacinthacines.

  从d-木糖衍生的多羟基环状硝酮出发，成功合成了5-epi-(-)-风信子素A3和(-)-风信子素A3。我们的合成策略可能普遍且灵活，适用于合成5-烷基-风信子素两种异构体。
• Design and Synthesis of Labystegines, Hybrid Iminosugars from LAB and Calystegine, as Inhibitors of Intestinal α-Glucosidases: Binding Conformation and Interaction for ntSI
  作者：Atsushi Kato、Zhao-Lan Zhang、Hong-Yao Wang、Yue-Mei Jia、Chu-Yi Yu、Kyoko Kinami、Yuki Hirokami、Yutaro Tsuji、Isao Adachi、Robert J. Nash、George W. J. Fleet、Jun Koseki、Izumi Nakagome、Shuichi Hirono

  DOI：10.1021/acs.joc.5b00342

  日期：2015.5.1

  This paper identifies the required configuration and orientation of alpha-glucosidase inhibitors, miglitol, alpha-1-C-butyl-DNJ, and alpha-1-C-butyl-LAB for binding to ntSI (isomaltase). Molecular dynamics (MD) calculations suggested that the flexibility around the keyhole of ntSI is lower than that of ctSI (sucrase). Furthermore, a molecular-docking study revealed that a specific binding orientation with a CH-pi interaction (Trp370 and Phe648) is a requirement for achieving a strong affinity with ntSI. On the basis of these results, a new class of nortropane-type iminosugars, labystegines, hybrid iminosugars of LAB and calystegine, have been designed and synthesized efficiently from sugar-derived cyclic nitrones with intramolecular 1,3-dipolar cycloaddition or samarium iodide catalyzed reductive coupling reaction as the key step. Biological evaluation showed that our newly designed 3(S)-hydroxy labystegine (6a) inherited the selectivity against intestinal alpha-glucosidases from LAB, and its inhibition potency was 10 times better than that of miglitol. Labystegine, therefore, represents a promising new class of nortropane-type iminosugar for improving postprandial hyperglycemia.