ethyl (3R,4R,5S)-4-acetamido-5-[N2,N3-bis(tert-butoxycarbonyl)guanidino]-3-(1-ethylpropoxy)-1-cyclohexene-1-phosphonate ammonium salt | 1122581-43-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: ethyl (3R,4R,5S)-4-acetamido-5-[N2,N3-bis(tert-butoxycarbonyl)guanidino]-3-(1-ethylpropoxy)-1-cyclohexene-1-phosphonate ammonium salt
• 英文别名: Ethyl (3r,4r,5s)-4-acetamido-5-guanidinyl-3-(1-ethylpropoxy)-1-cyclohexene-1-phosphonate ammonium salt；azanium;[(3R,4R,5S)-4-acetamido-5-(diaminomethylideneamino)-3-pentan-3-yloxycyclohexen-1-yl]-ethoxyphosphinate
• CAS: 1122581-43-4
• 化学式: C₁₆H₃₁N₄O₅P*H₃N
• 分子量: 407.45
• InChiKey: ZKUNHKFFXNYURA-ONAKXNSWSA-N

物化性质

• 熔点：
  70-72 °C

计算性质

• 辛醇/水分配系数(LogP)：
  1.17
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  153
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  [(3R,4R,5S)-4-acetamido-5-(diaminomethylideneamino)-3-pentan-3-yloxycyclohexen-1-yl]-ethoxyphosphinic acid 在 碳酸氢铵 作用下， 以 水 为溶剂， 反应 1.0h， 生成 ethyl (3R,4R,5S)-4-acetamido-5-[N2,N3-bis(tert-butoxycarbonyl)guanidino]-3-(1-ethylpropoxy)-1-cyclohexene-1-phosphonate ammonium salt
  参考文献：
  名称：

  [EN] SYNTHESIS OF OSELTAMIVIR CONTAINING PHOSPHONATE CONGENERS WITH ANTI-INFLUENZA ACTIVITY
  [FR] SYNTHÈSE D'OSELTAMIVIR CONTENANT DES CONGÉNÈRES DE PHOSPHONATE AYANT UNE ACTIVITÉ ANTI-GRIPPALE

  摘要：

  公开号：

  WO2009029888A3

文献信息

• SYNTHESIS OF OSELTAMIVIR CONTAINING PHOSPHONATE CONGENERS WITH ANTI-INFLUENZA ACTIVITY
  申请人：Wong Chi-Huey

  公开号：US20100113397A1

  公开（公告）日：2010-05-06

  Novel phosphonate compounds are described. The compounds have activity as neuraminidase inhibitors against wild-type and H274Y mutant of H1N1 and H5N1 viruses. The present disclosure also provides an enantioselective synthetic route to known neuraminidase inhibitors oseltamivir and the anti-flu drug Tamiflu®, as well as novel phosphonate compounds, via D-xylose. Another efficient and flexible synthesis of Tamiflu and the highly potent neuraminidase inhibitor Tamiphosphor was also achieved in 11 steps and >20% overall yields from the readily available fermentation product (1S-cis)-3-bromo-3,5-cyclohexadiene-1,2-diol. Most of the reaction intermediates were obtained as crystals without tedious purification procedures. The key transformations include an initial regio- and stereoselective bromoamidation of a bromoarene cis-dihydrodiol, as well as the final palladium-catalyzed carbonylation and phosphonylation.

  本文描述了新型膦酸盐化合物。这些化合物对H1N1和H5N1病毒的野生型和H274Y突变体具有神经氨酸酶抑制剂活性。本公开还提供了一种手性选择性的合成路线，可通过D-木糖合成已知的神经氨酸酶抑制剂奥司他韦和抗流感药物达菲®，以及新型膦酸盐化合物。另外，还通过11个步骤和>20％的总收率，从易得到的发酵产物（1S-cis）-3-溴-3,5-环己二烯-1,2-二醇中实现了达菲和高效神经氨酸酶抑制剂Tamiphosphor的有效灵活合成。大多数反应中间体都以晶体形式获得，无需繁琐的纯化程序。关键的转化包括最初的区域和立体选择性的溴胺化反应，以及最后的钯催化的羰基化和膦酸盐化反应。
• Synthesis of oseltamivir containing phosphonate congeners with anti-influenza activity
  申请人：Academia Sinica

  公开号：US07888337B2

  公开（公告）日：2011-02-15

  Novel phosphonate compounds are described. The compounds have activity as neuraminidase inhibitors against wild-type and H274Y mutant of H1N1 and H5N1 viruses. The present disclosure also provides an enantioselective synthetic route to known neuraminidase inhibitors oseltamivir and the anti-flu drug Tamiflu®, as well as novel phosphonate compounds, via D-xylose. Another efficient and flexible synthesis of Tamiflu and the highly potent neuraminidase inhibitor Tamiphosphor was also achieved in 11 steps and >20% overall yields from the readily available fermentation product (1S-cis)-3-bromo-3,5 -cyclohexadiene-1,2-diol. Most of the reaction intermediates were obtained as crystals without tedious purification procedures. The key transformations include an initial regio- and stereoselective bromoamidation of a bromoarene cis-dihydrodiol, as well as the final palladium-catalyzed carbonylation and phosphonylation.

  本文介绍了一种新型膦酸盐化合物。这些化合物对H1N1和H5N1病毒的野生型和H274Y突变体具有神经氨酸酶抑制剂活性。本公开还提供了一种手性选择性合成途径，通过D-木糖合成已知的神经氨酸酶抑制剂奥司他韦和抗流感药物达菲®，以及新型膦酸盐化合物。另外，还通过简单的11步反应和>20%的总收率，从易得的发酵产物（1S-cis）-3-溴-3,5-环己二烯-1,2-二醇中，实现了达菲和高效神经氨酸酶抑制剂Tamiphosphor的有效灵活合成。大部分反应中间体均为晶体，无需繁琐的纯化步骤。关键转化包括最初的区域和立体选择性的溴化酰胺化反应，以及最终的钯催化的羰基化和膦化反应。
• US7888337B2
  申请人：——

  公开号：US7888337B2

  公开（公告）日：2011-02-15
• [EN] SYNTHESIS OF OSELTAMIVIR CONTAINING PHOSPHONATE CONGENERS WITH ANTI-INFLUENZA ACTIVITY<br/>[FR] SYNTHÈSE D'OSELTAMIVIR CONTENANT DES CONGÉNÈRES DE PHOSPHONATE AYANT UNE ACTIVITÉ ANTI-GRIPPALE
  申请人：WONG CHI-HUEY

  公开号：WO2009029888A3

  公开（公告）日：2009-05-07