tert-butyl 7Z-acetylmethylene-3-methyl-1,1-dioxoceph-3-em-4-carboxylate | 1134181-24-0

• 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: tert-butyl 7Z-acetylmethylene-3-methyl-1,1-dioxoceph-3-em-4-carboxylate
• 英文别名: 7Z-acetylmethylene-3-methyl-1,1-dioxo-3-cepheme-4-carboxylic acid；tert-butyl (6R,7Z)-3-methyl-5,5,8-trioxo-7-(2-oxopropylidene)-5lambda6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate；tert-butyl (6R,7Z)-3-methyl-5,5,8-trioxo-7-(2-oxopropylidene)-5λ6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 1134181-24-0
• 化学式: C₁₅H₁₉NO₆S
• 分子量: 341.385
• InChiKey: FIDYQQYGPHMKEU-AGEOTTOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  106
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 7Z-acetylmethylene-3-methyl-1,1-dioxoceph-3-em-4-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (6R,7Z)-3-methyl-5,5,8-trioxo-7-(2-oxopropylidene)-5lambda6-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and cytotoxic properties of derivatives of the tert-butyl ester of 7-alkylidene-3-methyl-3-cepheme-4-carboxylic acid

  摘要：

  Sulfones of the tert-butyl esters of 7-arylmethylene-and 7-(2-furyl)methylene-3-methyl-3-cepheme-4-carboxylic acid were obtained by the condensation of the tert-butyl ester of 3-methyl-7-oxo-3-cepheme-4-carboxylic acid with arylmethylene-and 2-furylidenetriphenylphosphoranes and subsequent oxidation of the intermediate products by meta-chloroperbenzoic acid. The combination of the tert-butyl esters of 7E-bromomethylene-and 7,7-dibromomethylene-3-methyl-1,1-dioxo-3-cepheme-4-carboxylic acids with trimethylsilylacetylene under conditions of the Sonogashira reaction gave the tert-butyl esters of 3-methyl-1,1-dioxo-7E-(3-trimethylsilyl-2-propynylidene)-3-cepheme-4-carboxylic acid and 3-methyl-1,1-dioxo-7-[1,5-bis(trimethylsilyl)-1,4-pentadiyn-3-ylidene]-3-cepheme-4-carboxylic acid. The Vilsmeier reagent was used to incorporate the dimethylaminomethylene group at C-2 of the 7Z-and 7E-isomers of the tert-butyl ester of 7-(4-chlorophenyl)methylene-3-methyl-1,1-dioxo-3-cepheme-4-carboxylic acid. The cytotoxic properties of the derivatives of the tert-butyl ester of 7-alkylidene-3-methyl-3-cepheme-4-carboxylic acid in regard to cancer and normal cells in vitro depends on the structure and 7Z-or 7E-isomerism of the substituent in the 7-alkylidene group as well as the presence of a dimethylaminomethylene group at C-2 of the 3-cepheme system.

  DOI：

  10.1007/s10593-008-0099-0
• 作为产物：
  描述：

  tert-butyl 7Z-acetylmethylene-3-methylceph-3-em-4-carboxylate 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以78%的产率得到tert-butyl 7Z-acetylmethylene-3-methyl-1,1-dioxoceph-3-em-4-carboxylate
  参考文献：
  名称：

  Synthesis and stereoisomerism of derivatives of tert-butyl 7-alkylideneceph-3-em-4-carboxylate

  摘要：

  By condensation of tert-butyl 3-methyl-7-oxoceph-3-em-4-carboxylate and its 3-acetoxymethyl analog with acetylmethylenetriphenylphosphorane and 3-trimethylsilylpropyn-2-ylindenetriphenylphosphorane tert-butyl 7Z-acetylmethylene-3-methylceph-3-em-4-carboxylate and also 7Z-and 7E-isomers of tert-butyl 3-acetoxymethyl-7-(3-trimethylsilylpropyn-2-ylidene)ceph-3-em-4-carboxylates were synthesized. Oxidation of these compounds with 1 equivalent of meta-chloroperbenzoic acid gave their 1R-and 1S-sulfoxides, and oxidation with 2 equivalents gave the corresponding sulfones. According to data from H-1 NMR spectroscopy, the carbonyl of the beta-lactam descreens proton H-9 of the alkylidene group in the 7Z-isomers more strongly than in the 7E-isomers, shifting their signals to weaker field. Analogous shifts of the H-6 signal to weaker field was observed in the 1R-sulfoxides in comparison with that for the 1S-sulfoxide. These results were confirmed by X-ray crystallography of tert-butyl 7Z-acetylmethylene-3-methyl-1S-oxoceph-3-em-4-carboxylate and tert-butyl 7Z-acetylmethylene-3-methyl-1,1-dioxoceph-3-em-4-carboxy-late.

  DOI：

  10.1007/s10593-008-0067-8

文献信息

• Synthesis and cytotoxic activity of derivatives of the tert-butyl ester of 7Z-acetylmethylene-3-methyl-3-cephem-4-carboxylic acid
  作者：I. Potorocina、M. Vorona、G. Veinberg、I. Shestakova、I. Kanepe、M. Petrova、E. Liepinsh、E. Lukevics

  DOI：10.1007/s10593-009-0254-2

  日期：2009.2

  The condensation of the acetylmethylene group in the tert-butyl esters of 7Z-acetylmethylene-3-methyl-3-cephem-4-carboxylic acid and 7Z-acetylmethylene-3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid and in 7Z-acetylmethylene-3-methylene-1,1-dioxo-3-cephem with arylmethoxyamines and O-alkylation of the tert-butyl ester of 7Z-(2-hydroxyimino)propylidene-3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid using

  乙酰基亚甲基在7 Z-乙酰基亚甲基-3-甲基-3-cephem-4-羧酸和7 Z-乙酰基亚甲基-3-甲基-1,1-二氧代-3- cephem-的叔丁基酯中的缩合-4-羧酸和7 ž -acetylmethylene -3-亚甲基-1,1-二氧代-3-头孢烯与arylmethoxyamines和的O-烷基化叔7的丁基酯ž-（2-羟基亚氨基）亚丙基-3-甲基-1,1-二氧代-3-cephem-4-羧酸，使用取代的苄基溴化物和吡啶基甲基氯化物，以顺式和反异构形式得到这些化合物的芳基甲氧基亚氨基和吡啶基甲氧基亚氨基衍生物。使用Vilsmaier试剂将头孢烯系统的C-2处的N，N-二甲基氨基亚甲基引入7 Z- [2-（芳甲氧基亚氨基）亚丙基] -3-甲基-1,1-二氧杂的叔丁基酯中。-3-cephem-4-羧酸。随后使用羟胺对N，N-二甲基氨基亚甲基头孢烯的转化产生3 Z- [2-（抗芳基甲氧基亚氨基
• Synthesis and cytotoxic properties of derivatives of the tert-butyl ester of 7-alkylidene-3-methyl-3-cepheme-4-carboxylic acid
  作者：M. Vorona、I. Potorocina、G. Veinberg、I. Shestakova、I. Kanepe、E. Lukevics

  DOI：10.1007/s10593-008-0099-0

  日期：2008.6

  Sulfones of the tert-butyl esters of 7-arylmethylene-and 7-(2-furyl)methylene-3-methyl-3-cepheme-4-carboxylic acid were obtained by the condensation of the tert-butyl ester of 3-methyl-7-oxo-3-cepheme-4-carboxylic acid with arylmethylene-and 2-furylidenetriphenylphosphoranes and subsequent oxidation of the intermediate products by meta-chloroperbenzoic acid. The combination of the tert-butyl esters of 7E-bromomethylene-and 7,7-dibromomethylene-3-methyl-1,1-dioxo-3-cepheme-4-carboxylic acids with trimethylsilylacetylene under conditions of the Sonogashira reaction gave the tert-butyl esters of 3-methyl-1,1-dioxo-7E-(3-trimethylsilyl-2-propynylidene)-3-cepheme-4-carboxylic acid and 3-methyl-1,1-dioxo-7-[1,5-bis(trimethylsilyl)-1,4-pentadiyn-3-ylidene]-3-cepheme-4-carboxylic acid. The Vilsmeier reagent was used to incorporate the dimethylaminomethylene group at C-2 of the 7Z-and 7E-isomers of the tert-butyl ester of 7-(4-chlorophenyl)methylene-3-methyl-1,1-dioxo-3-cepheme-4-carboxylic acid. The cytotoxic properties of the derivatives of the tert-butyl ester of 7-alkylidene-3-methyl-3-cepheme-4-carboxylic acid in regard to cancer and normal cells in vitro depends on the structure and 7Z-or 7E-isomerism of the substituent in the 7-alkylidene group as well as the presence of a dimethylaminomethylene group at C-2 of the 3-cepheme system.
• Synthesis and stereoisomerism of derivatives of tert-butyl 7-alkylideneceph-3-em-4-carboxylate
  作者：M. Vorona、G. Veinberg、S. Belyakov、M. Petrova、E. Liepinsh、E. Lukevics

  DOI：10.1007/s10593-008-0067-8

  日期：2008.4

  By condensation of tert-butyl 3-methyl-7-oxoceph-3-em-4-carboxylate and its 3-acetoxymethyl analog with acetylmethylenetriphenylphosphorane and 3-trimethylsilylpropyn-2-ylindenetriphenylphosphorane tert-butyl 7Z-acetylmethylene-3-methylceph-3-em-4-carboxylate and also 7Z-and 7E-isomers of tert-butyl 3-acetoxymethyl-7-(3-trimethylsilylpropyn-2-ylidene)ceph-3-em-4-carboxylates were synthesized. Oxidation of these compounds with 1 equivalent of meta-chloroperbenzoic acid gave their 1R-and 1S-sulfoxides, and oxidation with 2 equivalents gave the corresponding sulfones. According to data from H-1 NMR spectroscopy, the carbonyl of the beta-lactam descreens proton H-9 of the alkylidene group in the 7Z-isomers more strongly than in the 7E-isomers, shifting their signals to weaker field. Analogous shifts of the H-6 signal to weaker field was observed in the 1R-sulfoxides in comparison with that for the 1S-sulfoxide. These results were confirmed by X-ray crystallography of tert-butyl 7Z-acetylmethylene-3-methyl-1S-oxoceph-3-em-4-carboxylate and tert-butyl 7Z-acetylmethylene-3-methyl-1,1-dioxoceph-3-em-4-carboxy-late.