(10S,13S)-13-(tert-Butyl-dimethyl-silanyloxymethyl)-3-hexyl-10-isopropyl-9-methyl-3,9,12-triaza-tricyclo[6.6.1.04,15]pentadeca-4,6,8(15)-trien-11-one | 756825-85-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (10S,13S)-13-(tert-Butyl-dimethyl-silanyloxymethyl)-3-hexyl-10-isopropyl-9-methyl-3,9,12-triaza-tricyclo[6.6.1.04,15]pentadeca-4,6,8(15)-trien-11-one
• CAS: 756825-85-1
• 化学式: C₂₉H₅₁N₃O₂Si
• 分子量: 501.828
• InChiKey: IACAVUUPXUHLOA-NKHIZBSDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.54
• 重原子数：
  35.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  44.81
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (10S,13S)-13-(tert-Butyl-dimethyl-silanyloxymethyl)-3-hexyl-10-isopropyl-9-methyl-3,9,12-triaza-tricyclo[6.6.1.04,15]pentadeca-4,6,8(15)-trien-11-one 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.67h， 以53%的产率得到(3R)-1-Hexylindolinelactam-V
  参考文献：
  名称：

  Synthesis, conformation and PKC isozyme surrogate binding of indolinelactam-Vs, new conformationally restricted analogues of (−)-indolactam-V

  摘要：

  New conformationally restricted analogues of tumor promoter (-)-indolactam-V (1), indolinelactam-Vs (8, 11) and their hexyl derivatives at position 1 or 7 (9, 10, 12, 13), were synthesized from 1. (3R)-Indolinelactam-V (8) adopted a conformation similar to the twist form of 1 with a cis amide, while the conformation of (3S)-indolinelactam-V (11) was close to that of the sofa form of 1 with a trans amide. 7-Hexyl derivatives of 8 and 11 (10, 13) showed binding affinities for Cl domains of protein kinase C (PKC) isozymes compared to 1, but exhibited little selectivity among these PKC isozymes. However, introduction of the hexyl group at position 1 of 8 and 11 significantly enhanced their binding selectivity for novel PKC isozymes. The best selectivity for novel PKC isozymes was observed in (3S)-1-hexylindolinelactam-V (12) with a sofa-like conformation. These results suggest that a sofa-restricted analogue of 1 with a hydrophobic chain at an appropriate position would be a promising lead for designing agents with a high selectivity for novel PKC isozymes. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.08.081
• 作为产物：
  描述：

  (-)-14-O-TBDMS-indolactam-V 在 sodium hydride 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (10S,13S)-13-(tert-Butyl-dimethyl-silanyloxymethyl)-3-hexyl-10-isopropyl-9-methyl-3,9,12-triaza-tricyclo[6.6.1.04,15]pentadeca-4,6,8(15)-trien-11-one
  参考文献：
  名称：

  Synthesis, conformation and PKC isozyme surrogate binding of indolinelactam-Vs, new conformationally restricted analogues of (−)-indolactam-V

  摘要：

  New conformationally restricted analogues of tumor promoter (-)-indolactam-V (1), indolinelactam-Vs (8, 11) and their hexyl derivatives at position 1 or 7 (9, 10, 12, 13), were synthesized from 1. (3R)-Indolinelactam-V (8) adopted a conformation similar to the twist form of 1 with a cis amide, while the conformation of (3S)-indolinelactam-V (11) was close to that of the sofa form of 1 with a trans amide. 7-Hexyl derivatives of 8 and 11 (10, 13) showed binding affinities for Cl domains of protein kinase C (PKC) isozymes compared to 1, but exhibited little selectivity among these PKC isozymes. However, introduction of the hexyl group at position 1 of 8 and 11 significantly enhanced their binding selectivity for novel PKC isozymes. The best selectivity for novel PKC isozymes was observed in (3S)-1-hexylindolinelactam-V (12) with a sofa-like conformation. These results suggest that a sofa-restricted analogue of 1 with a hydrophobic chain at an appropriate position would be a promising lead for designing agents with a high selectivity for novel PKC isozymes. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.08.081