methyl (2E,4R)-4-[(tert-butyldimethylsilyl)oxy]-4-{(1'R,2'S,4'S)-4'-[(tert-butyldimethylsilyl)oxy]-2'-[(1''E,6''S)-6''-hydroxyhept-1''-en-1''-yl]cyclopentyl}but-2-enoate | 1446488-71-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl (2E,4R)-4-[(tert-butyldimethylsilyl)oxy]-4-{(1'R,2'S,4'S)-4'-[(tert-butyldimethylsilyl)oxy]-2'-[(1''E,6''S)-6''-hydroxyhept-1''-en-1''-yl]cyclopentyl}but-2-enoate
• 英文别名: methyl (E,4R)-4-[tert-butyl(dimethyl)silyl]oxy-4-[(1R,2S,4S)-4-[tert-butyl(dimethyl)silyl]oxy-2-[(E,6S)-6-hydroxyhept-1-enyl]cyclopentyl]but-2-enoate
• CAS: 1446488-71-6
• 化学式: C₂₉H₅₆O₅Si₂
• 分子量: 540.932
• InChiKey: SOEGPWJVVABQMF-UBARXSOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.63
• 重原子数：
  36
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (2E,4R)-4-[(tert-butyldimethylsilyl)oxy]-4-{(1'R,2'S,4'S)-4'-[(tert-butyldimethylsilyl)oxy]-2'-[(1''E,6''S)-6''-hydroxyhept-1''-en-1''-yl]cyclopentyl}but-2-enoate 在 甲醇 、 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) 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 42.0h， 生成 (1R,6S,11aS,13S,14aR)-1,13-bis{[tert-butyl(dimethyl)silyl]oxy}-6-vinyl-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
• 作为产物：
  描述：

  布雷非德菌素 A 在 咪唑 、 4-二甲氨基吡啶 、 sodium methylate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 methyl (2E,4R)-4-[(tert-butyldimethylsilyl)oxy]-4-{(1'R,2'S,4'S)-4'-[(tert-butyldimethylsilyl)oxy]-2'-[(1''E,6''S)-6''-hydroxyhept-1''-en-1''-yl]cyclopentyl}but-2-enoate
  参考文献：
  名称：

  从布雷菲德菌素A合成3-氮杂双环[4.3.0]壬烷骨架

  摘要：

  布雷菲德菌素A（BFA）是一种真菌代谢产物，显示出广泛的生物学活性，使其成为药物发现的有吸引力的靶标。为了探索BFA支架的生物学潜力，提出了一种胺大环靶3。为了进行访问，我们将BFA分解为较小的构件，以准备再生大内酯。然后，这些实体可用于合成具有各种新结构特征的新布雷菲德菌素类似物，用于生物学测试。为了克服供应问题，采用了卡门氏青霉的大规模发酵工艺，产生了4.5千克的BFA。产生了新的N- BFA型衍生物，在此我们描述了两个新支架12和14的合成从BFA中分六个步骤提取，收率分别为24％和17％。甲反式-融合双环cyclopentanoid哌啶脚手架16可以从可以产生12，其可以充当有价值的新的支架用于新颖类似于天然产物的化合物的合成。

  DOI：

  10.1016/j.tetlet.2020.152006

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.
• The synthesis of 3-azabicyclo[4.3.0]nonane scaffolds from brefeldin A
  作者：Brooke Swaney、Andreas Luxenburger、Nigel T. Lucas、Bill C. Hawkins、Simon F.R. Hinkley

  DOI：10.1016/j.tetlet.2020.152006

  日期：2020.6

  discovery. To explore the biological potential of the BFA scaffold an amine-macrocycle target 3 was proposed. To access, we dissembled BFA into smaller building blocks in preparation for regenerating the macro-lactone. These entities can then be used to synthesise new brefeldin analogues with various new structural features for biological testing. To overcome supply issues a scaled fermentation process of Penicillium

  布雷菲德菌素A（BFA）是一种真菌代谢产物，显示出广泛的生物学活性，使其成为药物发现的有吸引力的靶标。为了探索BFA支架的生物学潜力，提出了一种胺大环靶3。为了进行访问，我们将BFA分解为较小的构件，以准备再生大内酯。然后，这些实体可用于合成具有各种新结构特征的新布雷菲德菌素类似物，用于生物学测试。为了克服供应问题，采用了卡门氏青霉的大规模发酵工艺，产生了4.5千克的BFA。产生了新的N- BFA型衍生物，在此我们描述了两个新支架12和14的合成从BFA中分六个步骤提取，收率分别为24％和17％。甲反式-融合双环cyclopentanoid哌啶脚手架16可以从可以产生12，其可以充当有价值的新的支架用于新颖类似于天然产物的化合物的合成。