(1R,6R,11aS,13S,14aR)-1,13-dihydroxy-6-[2-(1-naphthyl)ethyl]-1,6,7,8,9,11a,12,13,14,14a-decahydro-4H-cyclopenta[f]oxacyclotridecin-4-one | 1446489-00-4

• 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: (1R,6R,11aS,13S,14aR)-1,13-dihydroxy-6-[2-(1-naphthyl)ethyl]-1,6,7,8,9,11a,12,13,14,14a-decahydro-4H-cyclopenta[f]oxacyclotridecin-4-one
• 英文别名: (1R,2R,3E,7R,11E,13S,15S)-2,15-dihydroxy-7-(2-naphthalen-1-ylethyl)-6-oxabicyclo[11.3.0]hexadeca-3,11-dien-5-one
• CAS: 1446489-00-4
• 化学式: C₂₇H₃₂O₄
• 分子量: 420.549
• InChiKey: MJJBGCXYQKBMCD-QFAKEOTJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 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 、 palladium di-μ-chlorobis (η-allyl) 、 双(三甲基硅烷基)氨基钾 、 potassium hydrogencarbonate 、 N-甲基吗啉氧化物 、 triethylamine tris(hydrogen fluoride) 、 9-硼双环[3.3.1]壬烷 、 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 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 62.58h， 生成 (1R,6R,11aS,13S,14aR)-1,13-dihydroxy-6-[2-(1-naphthyl)ethyl]-1,6,7,8,9,11a,12,13,14,14a-decahydro-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

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.