t-butyl 7α-amino-3-methyl-3-cephem-4-carboxylate | 33610-06-9

• 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: t-butyl 7α-amino-3-methyl-3-cephem-4-carboxylate
• 英文别名: tert-butyl 7β-amino-3-deacetoxycephalosporanate；t-butyl 7β-amino-3-methyl-3-cephem-4-carboxylate；(6R)-7t-amino-3-methyl-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid tert-butyl ester；t-butyl(6R,7R)-7-amino-3-methyl-ceph-3-em-4-carboxylate；tert-butyl (6R,7R)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 33610-06-9
• 化学式: C₁₂H₁₈N₂O₃S
• 分子量: 270.353
• InChiKey: NNAIJPHLCFGSIW-GMSGAONNSA-N

物化性质

• 沸点：
  448.3±45.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  97.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  t-butyl 7α-amino-3-methyl-3-cephem-4-carboxylate 以 甲醇 为溶剂， 生成 (6R)-7t-benzylideneamino-3-methyl-7c-methylsulfanyl-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Stereospecific synthesis of C-6(7) methoxypenicillin and cephalosporin derivatives

  摘要：

  DOI：

  10.1021/jo00956a027
• 作为产物：
  描述：

  (6R)-3-methyl-8-oxo-7t-phthalimido-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid tert-butyl ester 在 sodium sulfide 、 N,N'-二环己基碳二亚胺 、 肼 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 生成 t-butyl 7α-amino-3-methyl-3-cephem-4-carboxylate
  参考文献：
  名称：

  来信：氮杂环丁酮抗生素。十四。从酸和碱敏感化合物中除去邻苯二甲酰基保护基。

  摘要：

  DOI：

  10.1021/ja00852a044

文献信息

• Synthesis of amino acid and 4,5-dihydro-6H-1,3-thiazine derivatives for the preparation of cephalosporin compounds.
  作者：TOSHIHIKO HASHIMOTO、TAIICHIRO WATANABE、YOICHI KAWANO、TERUO TANAKA、TETSUO MIYADERA

  DOI：10.1248/cpb.28.2980

  日期：——

  Several β-hydroxy-α-halogeno-α-amino acid derivatives (3-5) were prepared from tert-butyl N-benzylideneglycinate (1) and α-haloketones or an α-haloaldehyde for utilization in the synthesis of 4, 5-dihydro-6H-1, 3-thiazine derivatives (7 and 12). An alternative thiazine synthesis starting from tert-butyl glycinate (13) was found to proceed stereoselectively, giving rise to 12a. The two thiazine derivatives 7 and 12a were converted into cephalosporin derivatives (10 and 17, respectively) by reaction with azidoacetyl chloride. The 7-azido-3-methylcephem derivative (17) was further led to 7-aminodeacetoxycephalosporanic acid (7-ADCA, 22).

  几个β-羟基-α-卤代-α-氨基酸衍生物（3-5）是由叔丁基N-苄亚基甘氨酸（1）与α-卤代酮或α-卤代醛反应制备的，用于合成4, 5-二氢-6H-1, 3-噻嗪衍生物（7和12）。从叔丁基甘氨酸（13）出发的另一种噻嗪合成发现以立体选择性进行，生成12a。两个噻嗪衍生物7和12a通过与叠氮乙酰氯反应转化为头孢菌素衍生物（10和17）。7-叠氮-3-甲基头孢菌素衍生物（17）进一步转化为7-氨基去乙酰氧基头孢菌素酸（7-ADCA, 22）。
• 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。
• 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。
• Cephalosporines a chaines amino-2 thiazolyl-4 acetyles
  作者：R. Bucourt、R. Heymes、A. Lutz、L. Pénasse、J. Perronnet

  DOI：10.1016/0040-4020(78)89034-6

  日期：1978.1

  The syntheses of 2-(2-amino-4-thiazolyl) 2-(hydroxy or alkoxy)-imino acetic acid derivatives, with the anti (E) and syn (Z) configurations, are described. By means of these compounds, the acylation of the amino-group of 7β-amino cephalosporanic acid (7-ACA) has been achieved. The two resulting series of cephalosporin derivatives-anti and syn-are markedly different with respect to their antibiotic activity

  描述了具有反（E）和顺（Z）构型的2-（2-氨基-4-噻唑基）2-（羟基或烷氧基）-亚氨基乙酸衍生物的合成。通过这些化合物，已经实现了7β-氨基头孢烷酸（7-ACA）的氨基的酰化。这两个由此带来的一系列的头孢derivatives-防和顺式相对于它们的抗菌活性-are明显不同。一些合成化合物具有迄今为止所观察到的最高的抗菌活性。
• Reactions of cephalosporin sulfones 3. Synthesis of 2-phenylhydrazonocephem-sulfones. A new potential entry to 2-aminocephems
  作者：Tamas E. Gunda、Gyula Batta

  DOI：10.1002/jhet.5570430128

  日期：2006.1

  Reaction of cephem sulfones 1a-e with aryldiazonium salts gives the 2-azo compounds which immediately rearrange into the corresponding 2-hydrazono derivatives 2a-e.

  头孢砜砜1a-e与芳基重氮盐的反应产生了2-偶氮化合物，该化合物立即重排为相应的2-肼基衍生物2a-e。