methyl 5-acetamido-4-(morpholin-4-yl)-7,8,9-tri-O-acetyl-3,4,5-trideoxy-D-glycero-β-D-galacto-non-2-ulopyranosidonate | 943982-34-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 5-acetamido-4-(morpholin-4-yl)-7,8,9-tri-O-acetyl-3,4,5-trideoxy-D-glycero-β-D-galacto-non-2-ulopyranosidonate
• 英文别名: methyl (2S,4S,5R,6R)-5-acetamido-2-hydroxy-4-morpholin-4-yl-6-[(1S,2R)-1,2,3-triacetyloxypropyl]oxane-2-carboxylate
• CAS: 943982-34-1
• 化学式: C₂₂H₃₄N₂O₁₂
• 分子量: 518.518
• InChiKey: AMIOUHZHGIQJLJ-QDRUEPRISA-N

物化性质

• 沸点：
  629.7±55.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  176
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  methyl 5-acetamido-4-(morpholin-4-yl)-7,8,9-tri-O-acetyl-3,4,5-trideoxy-D-glycero-β-D-galacto-non-2-ulopyranosidonate 在 三氟乙酸酐 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 0.25h， 以80%的产率得到methyl 5-acetamido-2,6-anhydro-4-(morpholin-4-yl)-7,8,9-tri-O-acetyl-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enonate
  参考文献：
  名称：

  简单合成神经氨酸的N-全氟酰化和N-酰化的糖基，在4α位带有环状氨基取代基，可能是唾液酸酶的抑制剂†

  摘要：

  一种简单的合成N-全氟酰化和N-酰化糖基的方法神经氨酸，与仲环胺（吗啉 或者 哌啶）在4α位置已建立，从过乙酰化的N-乙酰神经氨酸甲酯开始，依次经历其直接N-酰化反应，然后进行C-4胺化，β消除和对N的选择性水解酯功能，而不会影响敏感的全氟酰胺。

  DOI：

  10.1039/c2ob07015d
• 作为产物：
  描述：

  吗啉 、 4,7,8,9-四-O-乙酰基-N-乙酰神经氨酸甲酯 以 吡啶 为溶剂， 反应 12.0h， 以100%的产率得到methyl 5-acetamido-4-(morpholin-4-yl)-7,8,9-tri-O-acetyl-3,4,5-trideoxy-D-glycero-β-D-galacto-non-2-ulopyranosidonate
  参考文献：
  名称：

  Simultaneous stereoselective 4-amination with cyclic secondary amines and 2-O-deacetylation of peracetylated sialic acid derivatives

  摘要：

  Treatment of methyl 5-acetamido-2,4,7,8,9-penta-O-acetyl-3,5-dideoxy-beta-L-glycero-D-galacto-2-nonulopyranosidonate (1) with cyclic secondary amines in pyridine at room temperature for 24 h afforded unusual products (2a-g). Related experiments were carried out to explain the formation of 4-amination and 2-O-deacetylation of peracetylated sialic acid derivatives (2a-g). This reaction may provide a new strategy for the preparation of Zanamivir analogues as neuraminidase inhibitors for anti-H5N1 subtype of avian influenza virus (AIV). (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2007.04.023

文献信息

• Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities
  作者：Deju Ye、Woo-Jin Shin、Ning Li、Wei Tang、Enguang Feng、Jian Li、Pei-Lan He、Jian-Ping Zuo、Hanjo Kim、Ky-Youb Nam、Weiliang Zhu、Baik-Lin Seong、Kyoung Tai No、Hualiang Jiang、Hong Liu

  DOI：10.1016/j.ejmech.2012.06.033

  日期：2012.8

  With the introduction of bioisosteres of the guanidinium group together with scaffold hopping, 35 zanamivir analogs with C-4-modification were synthesized, and their inhibitory activities against both group-1 and group-2 neuraminidase (H5N1 and H3N2) were determined. Compound 026 exerts the most potency, with IC50 values of 0.58 and 2.72 mu M against N2 and N1, respectively. Further preliminary anti-avian influenza virus (AIV, H5N1) activities against infected MDCK cells were evaluated, and D5 exerts similar to 58% protective against AIV infection, which was comparable to zanamivir (similar to 67%). In a rat pharmacokinetic study, compound D5 showed an increased plasma half-life (t(1/2)) compared to zanamivir following either intravenous or oral administration. This study may represent a new start point for the future development of improved anti-AIV agents. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Efficient Dehydrative Sialylation of C-4-Aminated Sialyl-Hemiketal Donors with Ph₂SO/Tf₂O
  作者：Deju Ye、Wenfeng Liu、Dengyou Zhang、Enguang Feng、Hualiang Jiang、Hong Liu

  DOI：10.1021/jo802396a

  日期：2009.2.20

  An efficient approach to the dehydrative sialylation of various substrates with C-4-aminated sialyl-hemiketal donors by using the reagent combination of diphenyl sulfoxide and triflic anhydride is reported. By using a C-4-hindered non-nucleophilic amine auxiliary, excellent yields and high alpha-stereoselectivities were obtained for coupling with a wide range of primary and secondary acceptors.