methyl (2S,4S,5R,6R)-5-acetamido-2-hydroxy-4-(4-phenylpiperazin-1-yl)-6-[(1S,2R)-1,2,3-triacetyloxypropyl]oxane-2-carboxylate | 943982-39-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2S,4S,5R,6R)-5-acetamido-2-hydroxy-4-(4-phenylpiperazin-1-yl)-6-[(1S,2R)-1,2,3-triacetyloxypropyl]oxane-2-carboxylate
• CAS: 943982-39-6
• 化学式: C₂₈H₃₉N₃O₁₁
• 分子量: 593.631
• InChiKey: AMLWXFKVZHKBEP-LJXJJVDOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  42
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  170
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  methyl (2S,4S,5R,6R)-5-acetamido-2-hydroxy-4-(4-phenylpiperazin-1-yl)-6-[(1S,2R)-1,2,3-triacetyloxypropyl]oxane-2-carboxylate 在 吡啶 、 4-二甲氨基吡啶 、 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 生成 methyl 5-acetamido-4-(4-phenylpiperazin-1-yl)-6-(1,2,3-triacetoxypropyl)-5,6-dihydro-4H-pyran-2-carboxylate
  参考文献：
  名称：

  Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2012.06.033
• 作为产物：
  描述：

  N-苯基哌嗪 、 (1S,2R)-1-((2R,3R,4S,6R)-3-acetamido-4,6-diacetoxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate 在 吡啶 作用下， 生成 methyl (2S,4S,5R,6R)-5-acetamido-2-hydroxy-4-(4-phenylpiperazin-1-yl)-6-[(1S,2R)-1,2,3-triacetyloxypropyl]oxane-2-carboxylate
  参考文献：
  名称：

  Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2012.06.033

文献信息

• Simultaneous stereoselective 4-amination with cyclic secondary amines and 2-O-deacetylation of peracetylated sialic acid derivatives
  作者：Deju Ye、Jian Li、Jian Zhang、Hong Liu、Hualiang Jiang

  DOI：10.1016/j.tetlet.2007.04.023

  日期：2007.6

  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.
• 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.