t-Butyl-7α-methoxy-3-methyl-7β-phenoxyacetamido-3-cephem-4-carboxylat | 64394-95-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: t-Butyl-7α-methoxy-3-methyl-7β-phenoxyacetamido-3-cephem-4-carboxylat
• 英文别名: (6R)-7c-methoxy-3-methyl-8-oxo-7t-(2-phenoxy-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid tert-butyl ester；tert-butyl (6R,7S)-7-methoxy-3-methyl-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 64394-95-2
• 化学式: C₂₁H₂₆N₂O₆S
• 分子量: 434.513
• InChiKey: FSJQVJLWSOAGKA-CTNGQTDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (R)-3-methyl-7-(4-nitro-phenylsulfanylimino)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid tert-butyl ester 以 四氢呋喃 、 甲醇 为溶剂， 生成 t-Butyl-7α-methoxy-3-methyl-7β-phenoxyacetamido-3-cephem-4-carboxylat
  参考文献：
  名称：

  A novel synthetic route to 7.ALPHA.-methoxycephalosporins.

  摘要：

  将7β-磺酰胺头孢菌素7与二氧化锰等氧化剂反应得到亚砜亚胺8，然后用甲醇锂容易甲氧基化得到7α-甲氧基-磺酰胺9。7α-甲氧基-磺酰胺头孢菌素9与碘化钠反应转化为游离胺10。将10酰化得到头霉素衍生物11。这种方法也成功应用于青霉素系列，得到亚砜亚胺13，经甲氧基化得到目标产物6α-甲氧基-青霉素14和开环产物15。

  DOI：

  10.1248/cpb.27.2718

文献信息

• A synthesis of cephamycins from cephalosporins and related reactions.
  作者：TAKEO KOBAYASHI、KIMIO IINO、TETSUO HIRAOKA

  DOI：10.1248/cpb.27.2727

  日期：——

  The sulfinamides 3 were transformed to sulfenimines 4 by treatment with thionyl chloride and a weak base such as quinoline (or triethylamine). The sulfenimines 4 were methoxylated with lithium methoxide to give 7α-methoxysulfenamides 5, which were directly acylated with an acyl chloride to furnish cephamycin derivatives 6. There was a major difference between the acylation of 7α-methoxysulfenamides 5 and that of the 7α-H derivatives 7. Reduction of the imines 4a with metal hydrides gave 7β-sulfenaminocephalosporins 12 together with a small amount of the 7α-isomers 13. The synthetic sequence 4a→12→14 provides a useful method for the isomerization of 7α-aminocephalosporins 17 to the corresponding 7β-isomers 18.

  用亚硫酰氯和弱碱（如喹啉或三乙胺）将亚磺酰胺 3 转化为亚磺酰亚胺 4。亚磺酰亚胺 4 与甲醇锂发生甲氧基化反应，生成 7α-甲氧基亚磺酰胺 5，然后直接与酰基氯发生酰基化反应，生成头霉素衍生物 6。7α-Methoxysulfenamides 5 的酰化过程与 7α-H 衍生物 7 的酰化过程有很大不同。用金属氢化物还原亚胺 4a，可得到 7β-亚磺酰胺头孢菌素 12 以及少量 7α 异构体 13。合成序列 4a→12→14 为 7α 氨基头孢菌素 17 异构化为相应的 7β 异构体 18 提供了有用的方法。
• A Synthesis of 7α-Methoxycephalosporins through Selenenamides
  作者：Takeo Kobayashi、Tetsuo Hiraoka

  DOI：10.1246/bcsj.52.3366

  日期：1979.11

  The o-nitrobenzeneselenenamides were oxidized with active manganese dioxide to give the irnines, which were converted to the 7α-methoxycephalosporins 3 by the reaction with lithium methoxide. The selenenamides 3 were acylated with phenoxyacetyl chloride to afford the desired cephamycin derivatives 4 via tertiary amide 5, which was not isolable. This methoxylation reaction was also carried out in penicillin

  邻硝基苯硒酰胺用活性二氧化锰氧化得到亚氨酸，后者通过与甲醇锂反应转化为 7α-甲氧基头孢菌素 3。硒酰胺 3 用苯氧基乙酰氯酰化，通过叔酰胺 5 得到所需的头霉素衍生物 4，其不可分离。该甲氧基化反应也在青霉素系列中进行，得到所需的 6α-甲氧基青霉素 8，尽管开环化合物 9 是主要产物。讨论了次磺酰胺和硒酰胺在酰化反应中的区别。
• US4162251A
  申请人：——

  公开号：US4162251A

  公开（公告）日：1979-07-24
• US4438265A
  申请人：——

  公开号：US4438265A

  公开（公告）日：1984-03-20
• A novel synthetic route to 7.ALPHA.-methoxycephalosporins.
  作者：TAKEO KOBAYASHI、TETSUO HIRAOKA

  DOI：10.1248/cpb.27.2718

  日期：——

  Treatment of 7β-sulfenamidocephalosporins 7 with an oxidizing agent such as active manganese dioxide gave the sulfenimines 8, which were easily methoxylated to the 7α-methoxy-sulfenamides 9 with lithium methoxide. The 7α-methoxy-sulfenamidocephalosporins 9 were converted to the free amine 10 by reaction with sodium iodide. Acylation of 10 afforded the cephamycin derivative 11. This method was also successfully applied to the penicillin series, leading to the sulfenimine 13, which was methoxylated to furnish the desired 6α-methoxy-penicillin 14 together with the ring-opened product 15.

  将7β-磺酰胺头孢菌素7与二氧化锰等氧化剂反应得到亚砜亚胺8，然后用甲醇锂容易甲氧基化得到7α-甲氧基-磺酰胺9。7α-甲氧基-磺酰胺头孢菌素9与碘化钠反应转化为游离胺10。将10酰化得到头霉素衍生物11。这种方法也成功应用于青霉素系列，得到亚砜亚胺13，经甲氧基化得到目标产物6α-甲氧基-青霉素14和开环产物15。