[(1S)-1-(4-bromo-1,3-thiazol-2-yl)-3-methylbutoxy]-tert-butyl-dimethylsilane | 1245503-23-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [(1S)-1-(4-bromo-1,3-thiazol-2-yl)-3-methylbutoxy]-tert-butyl-dimethylsilane
• CAS: 1245503-23-4
• 化学式: C₁₄H₂₆BrNOSSi
• 分子量: 364.422
• InChiKey: ZAWMZHMHUBKQDA-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.01
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  50.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [(1S)-1-(4-bromo-1,3-thiazol-2-yl)-3-methylbutoxy]-tert-butyl-dimethylsilane 、 N,N-二甲基甲酰胺 在 叔丁基锂 作用下， 以 乙醚 、 正戊烷 为溶剂， 反应 1.5h， 以70%的产率得到C₁₅H₂₇NO₂SSi
  参考文献：
  名称：

  Synthesis and evaluation of an Iejimalide-archazolid chimera

  摘要：

  Even though the macrolides of the iejimalide family are of marine origin, whereas those of the archazolid series derive from terrestrial myxobacteria, a comparison of their constitution, stereochemistry, and biological activity suggests that these natural products are close structural and functional relatives. Guided by this perception, compound 5 was prepared, which hybridizes the macrolactone core of iejimalide B (2) with the tail of archazolid A (3). The cytotoxicity profile of this chimera, as determined with a panel of 12 human cancer cell lines, corresponds to that of the parent compound 2, although its potency is lower. This outcome may be interpreted on the basis of molecular dynamics calculations, which suggest that the low energy conformations of 2 and 5 are similar but the energetic barriers between the relevant conformers are distinctly higher for the hybrid structure. The synthesis of 5 hinged on a regioselective functionalization of 2,4-dibromothiazole 6, a highly selective CBS-reduction of ketone 8, a Suzuki cross coupling of vinyl boronate 17 with the elaborate alkenyl iodide 16, and a productive closure of the macrocycle by RCM, which requires the selective activation of two out of eight double bonds present in the cyclization precursor 20 by the second-generation Grubbs catalyst 21. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2010.05.043
• 作为产物：
  描述：

  (S)-1-(4-bromothiazol-2-yl)-3-methylbutan-1-ol 、 叔丁基二甲硅基三氟甲磺酸酯 在 2,6-二甲基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以84%的产率得到[(1S)-1-(4-bromo-1,3-thiazol-2-yl)-3-methylbutoxy]-tert-butyl-dimethylsilane
  参考文献：
  名称：

  Synthesis and evaluation of an Iejimalide-archazolid chimera

  摘要：

  Even though the macrolides of the iejimalide family are of marine origin, whereas those of the archazolid series derive from terrestrial myxobacteria, a comparison of their constitution, stereochemistry, and biological activity suggests that these natural products are close structural and functional relatives. Guided by this perception, compound 5 was prepared, which hybridizes the macrolactone core of iejimalide B (2) with the tail of archazolid A (3). The cytotoxicity profile of this chimera, as determined with a panel of 12 human cancer cell lines, corresponds to that of the parent compound 2, although its potency is lower. This outcome may be interpreted on the basis of molecular dynamics calculations, which suggest that the low energy conformations of 2 and 5 are similar but the energetic barriers between the relevant conformers are distinctly higher for the hybrid structure. The synthesis of 5 hinged on a regioselective functionalization of 2,4-dibromothiazole 6, a highly selective CBS-reduction of ketone 8, a Suzuki cross coupling of vinyl boronate 17 with the elaborate alkenyl iodide 16, and a productive closure of the macrocycle by RCM, which requires the selective activation of two out of eight double bonds present in the cyclization precursor 20 by the second-generation Grubbs catalyst 21. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2010.05.043

文献信息

• Synthesis and evaluation of an Iejimalide-archazolid chimera
  作者：Emilie Moulin、Cristina Nevado、Julien Gagnepain、Gerhard Kelter、Heinz-Herbert Fiebig、Alois Fürstner

  DOI：10.1016/j.tet.2010.05.043

  日期：2010.8

  Even though the macrolides of the iejimalide family are of marine origin, whereas those of the archazolid series derive from terrestrial myxobacteria, a comparison of their constitution, stereochemistry, and biological activity suggests that these natural products are close structural and functional relatives. Guided by this perception, compound 5 was prepared, which hybridizes the macrolactone core of iejimalide B (2) with the tail of archazolid A (3). The cytotoxicity profile of this chimera, as determined with a panel of 12 human cancer cell lines, corresponds to that of the parent compound 2, although its potency is lower. This outcome may be interpreted on the basis of molecular dynamics calculations, which suggest that the low energy conformations of 2 and 5 are similar but the energetic barriers between the relevant conformers are distinctly higher for the hybrid structure. The synthesis of 5 hinged on a regioselective functionalization of 2,4-dibromothiazole 6, a highly selective CBS-reduction of ketone 8, a Suzuki cross coupling of vinyl boronate 17 with the elaborate alkenyl iodide 16, and a productive closure of the macrocycle by RCM, which requires the selective activation of two out of eight double bonds present in the cyclization precursor 20 by the second-generation Grubbs catalyst 21. (C) 2010 Elsevier Ltd. All rights reserved.