1-(isopropoxycarbonyloxy)ethyl (6R,7R)-3-(N,N-dimethylcarbamoyloxy)methyl-7-formamido-Δ²-cephem-4-carboxylate | 172665-31-5

• 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: 1-(isopropoxycarbonyloxy)ethyl (6R,7R)-3-(N,N-dimethylcarbamoyloxy)methyl-7-formamido-Δ²-cephem-4-carboxylate
• 英文别名: 1-propan-2-yloxycarbonyloxyethyl (6R,7R)-3-(dimethylcarbamoyloxymethyl)-7-formamido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate
• CAS: 172665-31-5
• 化学式: C₁₈H₂₅N₃O₉S
• 分子量: 459.477
• InChiKey: ZUJAVTGWCATYRM-IVYIRIEZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  166
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-(isopropoxycarbonyloxy)ethyl (6R,7R)-3-(N,N-dimethylcarbamoyloxy)methyl-7-formamido-Δ²-cephem-4-carboxylate 在 盐酸 、 甲烷磺酸 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 (6R,7R)-7-Amino-3-dimethylcarbamoyloxymethyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-3-ene-2-carboxylic acid; compound with trifluoro-acetic acid
  参考文献：
  名称：

  Studies on the Stability of .DELTA.2 and .DELTA.3 Cephem Esters. II. Comparative Stability Studies of .DELTA.2 and .DELTA.3 Cephems at Various pHs and the Degradation Process of .DELTA.2 Cephem Esters.

  摘要：

  酸条件下Δ2头孢菌素前药型酯（5a）的不稳定性促使我们研究了Δ3和Δ2头孢菌素在不同pH下的相对稳定性。与Δ3头孢菌素酯（4a）相比，Δ2头孢菌素酯5a在中性（pH 7）和酸性条件（1M HCl）下表现出明显的稳定性差异。在pH 7和1M HCl溶液中对Δ3（4c）和Δ2头孢菌素酸（5c）进行的比较研究表明，Δ2酸5c在pH 7时与Δ3酸4c同样稳定，而在1M HCl中5c的稳定性低于4c。降解产物的分离表明，C-4酯部分最初发生水解生成5c，随后进一步降解为极性更强的物质。这种不稳定性在其他类型的Δ2头孢菌素酯（5d-f）中也有观察到。这里我们报道了比较稳定性研究及其降解产物的阐明。

  DOI：

  10.1248/cpb.43.1866
• 作为产物：
  描述：

  1-碘乙基异丙基碳酸酯 在 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(isopropoxycarbonyloxy)ethyl (6R,7R)-3-(N,N-dimethylcarbamoyloxy)methyl-7-formamido-Δ²-cephem-4-carboxylate
  参考文献：
  名称：

  Studies on the Stability of .DELTA.2 and .DELTA.3 Cephem Esters. II. Comparative Stability Studies of .DELTA.2 and .DELTA.3 Cephems at Various pHs and the Degradation Process of .DELTA.2 Cephem Esters.

  摘要：

  酸条件下Δ2头孢菌素前药型酯（5a）的不稳定性促使我们研究了Δ3和Δ2头孢菌素在不同pH下的相对稳定性。与Δ3头孢菌素酯（4a）相比，Δ2头孢菌素酯5a在中性（pH 7）和酸性条件（1M HCl）下表现出明显的稳定性差异。在pH 7和1M HCl溶液中对Δ3（4c）和Δ2头孢菌素酸（5c）进行的比较研究表明，Δ2酸5c在pH 7时与Δ3酸4c同样稳定，而在1M HCl中5c的稳定性低于4c。降解产物的分离表明，C-4酯部分最初发生水解生成5c，随后进一步降解为极性更强的物质。这种不稳定性在其他类型的Δ2头孢菌素酯（5d-f）中也有观察到。这里我们报道了比较稳定性研究及其降解产物的阐明。

  DOI：

  10.1248/cpb.43.1866

文献信息

• Studies on the Stability of .DELTA.2 and .DELTA.3 Cephem Esters. I. Marked Difference in Stability between .DELTA.2 and .DELTA.3 Cephem Prodrug Esters and Application to the Preparation of Key Intermediates for Oral Cephem Synthesis.
  作者：Shigeto NEGI、Mototuske YAMANAKA、Yuki KOMATSU、Akihiko TSURUOKA、Itaru TSUKADA、Norio MINAMI

  DOI：10.1248/cpb.43.1998

  日期：——

  The esterification of Δ3-cephem-4-carboxylic acid sodium salt (1) with 1-iodoethyl isopropyl carbonate always afforded the Δ2 cephem ester (3) as an inseparable minor component. However, in the course of formamido cleavage reaction, the 7-amino-Δ2-cephem ester (5) was observed to be less stable than the Δ3 cephem ester (4), which led us to develop a practical synthetic process for Δ3 cephem esters, including a key intermediate of E1101, a new oral cephalosporin.

  1-iodoethyl isopropyl carbonate酯化Δ3-cephem-4-羧酸钠盐（1）时，总能得到作为不可分割的次要成分的Δ2 cephem酯（3）。然而，在甲酰氨基裂解反应过程中，观察到 7-氨基-Δ2-头孢酯（5）不如Δ3-头孢酯（4）稳定，这促使我们开发出一种实用的Δ3-头孢酯合成工艺，包括一种新型口服头孢菌素 E1101 的关键中间体。
• Studies on the Stability of .DELTA.2 and .DELTA.3 Cephem Esters. II. Comparative Stability Studies of .DELTA.2 and .DELTA.3 Cephems at Various pHs and the Degradation Process of .DELTA.2 Cephem Esters.
  作者：Shigeto NEGI、Motosuke YAMANAKA、Yuki KOMATSU、Akihiko TSURUOKA、Itaru TSUKADA、Norio MINAMI

  DOI：10.1248/cpb.43.1866

  日期：——

  The instability of Δ2 cephem prodrug-type ester (5a) under acidic conditions prompted us to investigate the comparative stability of Δ3 and Δ2 cephems at various pHs. The Δ2 cephem ester 5a was found to show marked instability under neutral (pH 7) and acidic conditions (1M HCl) compared with the Δ3 cephem ester (4a). A comparative study between Δ3 (4c) and Δ2 cephem acid (5c) at pH 7 and in 1M HCl solution showed that the Δ2 acid 5c was as stable as the Δ3 acid 4c pH 7, while 5c was less stable than 4c in 1M HCl. Isolation of the degraded compounds demonstrated that the C-4 ester moiety was hydrolyzed in the initial stage to afford 5c, which was further degraded to more polar substances. This instability was observed in other types of Δ2 cephem esters (5d-f). Here we report comparative stability studies and elucidation of the degradation products.

  酸条件下Δ2头孢菌素前药型酯（5a）的不稳定性促使我们研究了Δ3和Δ2头孢菌素在不同pH下的相对稳定性。与Δ3头孢菌素酯（4a）相比，Δ2头孢菌素酯5a在中性（pH 7）和酸性条件（1M HCl）下表现出明显的稳定性差异。在pH 7和1M HCl溶液中对Δ3（4c）和Δ2头孢菌素酸（5c）进行的比较研究表明，Δ2酸5c在pH 7时与Δ3酸4c同样稳定，而在1M HCl中5c的稳定性低于4c。降解产物的分离表明，C-4酯部分最初发生水解生成5c，随后进一步降解为极性更强的物质。这种不稳定性在其他类型的Δ2头孢菌素酯（5d-f）中也有观察到。这里我们报道了比较稳定性研究及其降解产物的阐明。