ethyl (3S,4R,5S,6S)-4-acetamido-6-acetyloxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-5-pentan-3-yloxycyclohexene-1-carboxylate | 208589-22-4

• 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: ethyl (3S,4R,5S,6S)-4-acetamido-6-acetyloxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-5-pentan-3-yloxycyclohexene-1-carboxylate
• CAS: 208589-22-4
• 化学式: C₂₃H₃₈N₂O₈
• 分子量: 470.563
• InChiKey: COKLQXVQRRYJNF-YRPNKDGESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  129
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl (3S,4R,5S,6S)-4-acetamido-6-acetyloxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-5-pentan-3-yloxycyclohexene-1-carboxylate 在 盐酸 、 copper(l) iodide 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 2.25h， 生成
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Carbocyclic Influenza Neuraminidase Inhibitors

  摘要：

  A series of influenza neuraminidase inhibitors with the cyclohexene scaffold containing lipophilic side chains have been synthesized anti evaluated for influenza A and B neuraminidase inhibitory activity. The size and geometry of side chains have been modified systematically in order to investigate structure-activity relationships of this class of compounds. The X-ray crystal structures of several analogues complexed with neuraminidase revealed that the lipophilic side chains bound to the hydrophobic pocket consisted of Glu276, Ala246, Arg224, and Ile222 of the enzyme active site. The structure-activity relationship studies of this series have also demonstrated remarkably different inhibitory potency between influenza A and B neuraminidase. This indicated that the lipophilic side chains had quite different hydrophobic interactions with influenza A and B neuraminidase despite their complete homology in the active site. Influenza B neuraminidase appeared to be much more sensitive toward the increased steric bulkiness of inhibitors compared to influenza A neuraminidase. From the extensive structure-activity relationship investigation reported in this article, GS 4071 emerged as one of the most potent influenza neuraminidase inhibitors against both influenza A and B strains.

  DOI：

  10.1021/jm980162u
• 作为产物：
  描述：

  ethyl (1S,2R,3S,4R,5S)-4-acetamido-1,2-dihydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-3-pentan-3-yloxycyclohexane-1-carboxylate 在 吡啶 、 4-二甲氨基吡啶 、 磺酰氯 、 硫酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 19.34h， 生成 ethyl (3S,4R,5S,6S)-4-acetamido-6-acetyloxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-5-pentan-3-yloxycyclohexene-1-carboxylate
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Carbocyclic Influenza Neuraminidase Inhibitors

  摘要：

  A series of influenza neuraminidase inhibitors with the cyclohexene scaffold containing lipophilic side chains have been synthesized anti evaluated for influenza A and B neuraminidase inhibitory activity. The size and geometry of side chains have been modified systematically in order to investigate structure-activity relationships of this class of compounds. The X-ray crystal structures of several analogues complexed with neuraminidase revealed that the lipophilic side chains bound to the hydrophobic pocket consisted of Glu276, Ala246, Arg224, and Ile222 of the enzyme active site. The structure-activity relationship studies of this series have also demonstrated remarkably different inhibitory potency between influenza A and B neuraminidase. This indicated that the lipophilic side chains had quite different hydrophobic interactions with influenza A and B neuraminidase despite their complete homology in the active site. Influenza B neuraminidase appeared to be much more sensitive toward the increased steric bulkiness of inhibitors compared to influenza A neuraminidase. From the extensive structure-activity relationship investigation reported in this article, GS 4071 emerged as one of the most potent influenza neuraminidase inhibitors against both influenza A and B strains.

  DOI：

  10.1021/jm980162u

文献信息

• [EN] METHOD OF FORMING OSELTAMIVIR AND DERIVATIVES THEREOF<br/>[FR] PROCÉDÉ DE FORMATION D'OSELTAMIVIR ET DE SES DÉRIVÉS ET APPLICATIONS CORRESPONDANTES
  申请人：UNIV NANYANG

  公开号：WO2009078813A1

  公开（公告）日：2009-06-25

  A process is provided for the synthesis of 4,5-diamino cyclohexene carboxylate ester (1): or a pharmaceutically acceptable salt thereof. R1 - R3 are a silyl-, an aliphatic, alicyclic, aromatic, arylaliphatic, or an arylalicyclic group. R4, R11 and R12 are H, a silyl-group, an aliphatic, alicyclic, aromatic, arylaliphatic, or an arylalicyclic group. 3,4-Dihydropyran compound (9): with R5 and R6 being suitable protecting groups, is reacted to form aldehyde (4): which is oxidized and converted to N-substituted carbamate (3): with R7 being a suitable protecting group. (3) is, via oxazolinidone (13): converted to azido carboxylate ester (2): and then to 4,5-diamino cyclohexene carboxylate ester (1).

  提供了一种用于合成4,5-二氨基环己烯羧酸酯（1）或其药用可接受的盐的过程。R1 - R3是硅基、脂肪、脂环、芳香、芳脂或芳环基团。R4、R11和R12是H、硅基、脂肪、脂环、芳香、芳脂或芳环基团。将3,4-二氢吡喃化合物（9）与适当的保护基R5和R6反应，形成醛（4），氧化并转化为N-取代的碳酸酯（3），其中R7是适当的保护基。通过噁唑啉二酮（13）将（3）转化为偶氮羧酸酯（2），然后转化为4,5-二氨基环己烯羧酸酯（1）。
• METHOD OF FORMING OSELTAMIVIR AND DERIVATIVES THEREOF
  申请人：Liu Xuewei

  公开号：US20110021762A1

  公开（公告）日：2011-01-27

  A process is provided for the synthesis of 4,5-diamino cyclohexene carboxylate ester (1): or a pharmaceutically acceptable salt thereof. R 1 -R 3 are a silyl-, an aliphatic, alicyclic, aromatic, arylaliphatic, or an arylalicyclic group. R 4 , R 11 and R 12 are H, a silyl-group, an aliphatic, alicyclic, aromatic, arylaliphatic, or an arylalicyclic group. 3,4-Dihydropyran compound (9): with R 5 and R 6 being suitable protecting groups, is reacted to form aldehyde (4): which is oxidized and converted to N-substituted carbamate (3): with R 7 being a suitable protecting group. (3) is, via oxazolinidone (13): converted to azido carboxylate ester (2): and then to 4,5-diamino cyclohexene carboxylate ester (1).

  本发明提供了一种合成4,5-二氨基环己烯羧酸酯（1）或其药学上可接受的盐的方法。其中R1-R3是硅基，脂肪基，脂环基，芳香基，芳脂基或芳环脂基。R4，R11和R12是氢，硅基，脂肪基，脂环基，芳香基，芳脂基或芳环脂基。将带有R5和R6适当保护基的3,4-二氢吡喃化合物（9）反应生成醛（4），然后氧化并转化为带有R7适当保护基的N-取代氨基甲酸酯（3）。通过氧杂环丙氨酮（13）将（3）转化为偶氮羧酸酯（2），然后再转化为4,5-二氨基环己烯羧酸酯（1）。
• US8304553B2
  申请人：——

  公开号：US8304553B2

  公开（公告）日：2012-11-06