methyl (2E,4R)-4-{[tert-Butyl(dimethyl)silyl]oxy}-4-{(1R,2S,4S)-4-{[tert-butyl(dimethyl)-silyl]oxy}-2-[(1E)-7,7,7-trifluoro-6-hydroxyhept-1-en-1-yl]cyclopentyl}but-2-enoate | 1446488-77-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: methyl (2E,4R)-4-{[tert-Butyl(dimethyl)silyl]oxy}-4-{(1R,2S,4S)-4-{[tert-butyl(dimethyl)-silyl]oxy}-2-[(1E)-7,7,7-trifluoro-6-hydroxyhept-1-en-1-yl]cyclopentyl}but-2-enoate
• 英文别名: (1R,2R,3E,7R,11E,13S,15S)-2,15-bis[[tert-butyl(dimethyl)silyl]oxy]-7-(trifluoromethyl)-6-oxabicyclo[11.3.0]hexadeca-3,11-dien-5-one
• CAS: 1446488-77-2
• 化学式: C₂₈H₄₉F₃O₄Si₂
• 分子量: 562.861
• InChiKey: AZNSNHHWIRCYSZ-FCRIWQKASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.56
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (2E,4R)-4-{[tert-Butyl(dimethyl)silyl]oxy}-4-{(1R,2S,4S)-4-{[tert-butyl(dimethyl)-silyl]oxy}-2-[(1E)-7,7,7-trifluoro-6-hydroxyhept-1-en-1-yl]cyclopentyl}but-2-enoate 在 triethylamine tris(hydrogen fluoride) 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以64%的产率得到(1R,6R,11aS,13S,14aR)-1,13-dihydroxy-6-(trifluoromethyl)-1,6,7,8,9,11a,12,13,14,14adecahydro-4H-cyclopenta[f]oxacyclotridecin-4-one
  参考文献：
  名称：

  Synthesis and Biological Properties of Novel Brefeldin A Analogues

  摘要：

  New brefeldin A (1) analogues were obtained by introducing a variety of substituents at C15. Most of the analogues exhibited significant biological activity. (15R)-Trifluoromethyl-nor-brefeldin A (3), (15R)-vinyl-nor-brefeldin A (5), their epimers 4 and 6 as well as (15S)-ethyl-nor-brefeldin A (2) were prepared from the key building blocks 12 or 24 by Julia-Kocienski olefination with tetrazolyl sulfones and subsequent macrolactonization. The vinyl derivative 5 allowed analogues to be synthesized by hydroboration and Suzuki-Miyaura coupling. The following biological properties were assessed: (a) inhibition of cell growth of human cancer cells (NCI), (b) induction of morphological changes of the Golgi apparatus of plant and mammalian cells, and (c) influence on the replication of the enterovirus CVB3. Furthermore, conformational aspects were studied by X-ray crystal structure analysis and molecular mechanics calculations, including docking of the analogues into the brefeldin A binding site of an Arf1/Sec7-complex.

  DOI：

  10.1021/jm400615g
• 作为产物：
  描述：

  布雷非德菌素 A 在 咪唑 、 甲醇 、 4-二甲氨基吡啶 、 potassium osmate(VI) dihydrate 、 sodium periodate 、 2,4,6-三氯苯甲酰氯 、 双(三甲基硅烷基)氨基钾 、 N-甲基吗啉氧化物 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 41.0h， 生成 methyl (2E,4R)-4-{[tert-Butyl(dimethyl)silyl]oxy}-4-{(1R,2S,4S)-4-{[tert-butyl(dimethyl)-silyl]oxy}-2-[(1E)-7,7,7-trifluoro-6-hydroxyhept-1-en-1-yl]cyclopentyl}but-2-enoate
  参考文献：
  名称：

  Synthesis and Biological Properties of Novel Brefeldin A Analogues

  摘要：

  New brefeldin A (1) analogues were obtained by introducing a variety of substituents at C15. Most of the analogues exhibited significant biological activity. (15R)-Trifluoromethyl-nor-brefeldin A (3), (15R)-vinyl-nor-brefeldin A (5), their epimers 4 and 6 as well as (15S)-ethyl-nor-brefeldin A (2) were prepared from the key building blocks 12 or 24 by Julia-Kocienski olefination with tetrazolyl sulfones and subsequent macrolactonization. The vinyl derivative 5 allowed analogues to be synthesized by hydroboration and Suzuki-Miyaura coupling. The following biological properties were assessed: (a) inhibition of cell growth of human cancer cells (NCI), (b) induction of morphological changes of the Golgi apparatus of plant and mammalian cells, and (c) influence on the replication of the enterovirus CVB3. Furthermore, conformational aspects were studied by X-ray crystal structure analysis and molecular mechanics calculations, including docking of the analogues into the brefeldin A binding site of an Arf1/Sec7-complex.

  DOI：

  10.1021/jm400615g

文献信息

• Synthesis and Biological Properties of Novel Brefeldin A Analogues
  作者：Kai Seehafer、Frank Rominger、Günter Helmchen、Markus Langhans、David G. Robinson、Başak Özata、Britta Brügger、Jeroen R. P. M. Strating、Frank J. M. van Kuppeveld、Christian D. Klein

  DOI：10.1021/jm400615g

  日期：2013.7.25

  New brefeldin A (1) analogues were obtained by introducing a variety of substituents at C15. Most of the analogues exhibited significant biological activity. (15R)-Trifluoromethyl-nor-brefeldin A (3), (15R)-vinyl-nor-brefeldin A (5), their epimers 4 and 6 as well as (15S)-ethyl-nor-brefeldin A (2) were prepared from the key building blocks 12 or 24 by Julia-Kocienski olefination with tetrazolyl sulfones and subsequent macrolactonization. The vinyl derivative 5 allowed analogues to be synthesized by hydroboration and Suzuki-Miyaura coupling. The following biological properties were assessed: (a) inhibition of cell growth of human cancer cells (NCI), (b) induction of morphological changes of the Golgi apparatus of plant and mammalian cells, and (c) influence on the replication of the enterovirus CVB3. Furthermore, conformational aspects were studied by X-ray crystal structure analysis and molecular mechanics calculations, including docking of the analogues into the brefeldin A binding site of an Arf1/Sec7-complex.