(1R,4S,7R,10S,13S,14R,15E,17E,19R,21S)-7-(3-bromo-4-hydroxybenzyl)-4-((S)-sec-butyl)-10-(2-hydroxypropan-2-yl)-19-methoxy-1,3,14,18-tetramethyl-13-phenyl-12,22-dioxa-3,6,9-triazabicyclo[19.1.0]docosa-15,17-diene-2,5,8,11-tetraone

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (1R,4S,7R,10S,13S,14R,15E,17E,19R,21S)-7-(3-bromo-4-hydroxybenzyl)-4-((S)-sec-butyl)-10-(2-hydroxypropan-2-yl)-19-methoxy-1,3,14,18-tetramethyl-13-phenyl-12,22-dioxa-3,6,9-triazabicyclo[19.1.0]docosa-15,17-diene-2,5,8,11-tetraone
• 英文别名: (1R,4S,7R,10S,13S,14R,15E,17E,19R,21S)-7-[(3-bromo-4-hydroxyphenyl)methyl]-4-[(2S)-butan-2-yl]-10-(2-hydroxypropan-2-yl)-19-methoxy-1,3,14,18-tetramethyl-13-phenyl-12,22-dioxa-3,6,9-triazabicyclo[19.1.0]docosa-15,17-diene-2,5,8,11-tetrone
• 化学式: C₄₂H₅₆BrN₃O₉
• 分子量: 826.825
• InChiKey: BBAXDMNJIJLFBM-ISPYYYCGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  55
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  167
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  D-3-bromotyrosine 在 氯化亚砜 、 palladium diacetate 、 碳酸氢钠 、 1-羟基苯并三唑 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 二乙胺 、 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 65.0h， 生成 (1R,4S,7R,10S,13S,14R,15E,17E,19R,21S)-7-(3-bromo-4-hydroxybenzyl)-4-((S)-sec-butyl)-10-(2-hydroxypropan-2-yl)-19-methoxy-1,3,14,18-tetramethyl-13-phenyl-12,22-dioxa-3,6,9-triazabicyclo[19.1.0]docosa-15,17-diene-2,5,8,11-tetraone
  参考文献：
  名称：

  Synthesis and biological evaluation of nannocystin analogues toward understanding the binding role of the (2R,3S)-Epoxide in nannocystin A

  摘要：

  Nannocystin A is a potent antiproliferative cyclodepsipeptide targeting eukaryotic translation elongation factor 1 alpha. To elucidate the binding role of its (2R,3S)-epoxide, we designed and synthesized a focused library of 10 nannocystin analogues. Variable temperature NMR experiments demonstrated the importance of the (2R,3S)-epoxide in controlling the macrocyclic conformation. Biological evaluation of these compounds against three typical cancer cell lines established a clear structure-activity relationship at the epoxide region, which was rationalized by comparing the superimposed conformations of different nannocystin analogues and in silico docking analysis. Our results showed that the (2R,3S)-epoxide of nannocystin A is mainly responsible for controlling the macrocyclic conformation, rather than binding directly to the target. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.012

文献信息

• Stereodivergent total synthesis of Br-nannocystins underpinning the polyketide (10R,11S) configuration as a key determinant of potency
  作者：Yunfeng Tian、Jiyan Wang、Wenjie Liu、Xiaoya Yuan、Yang Tang、Jing Li、Yue Chen、Weicheng Zhang

  DOI：10.1016/j.molstruc.2018.12.107

  日期：2019.4

  Abstract Continuing our investigation into the structure-activity relationship of antiproliferative macrocyclic nannocystins, we describe herein total synthesis of all four stereoisomers of Br-nannocystins as well as a simplified analogue varying at the polyketide C10 and C11 positions. Biological evaluation of these compounds against PANC1 cancer cell lines showed that both the (10R,11S) configuration

  摘要继续我们对抗增殖大环纳米囊藻毒素的构效关系的研究，我们在此描述了 Br-纳米囊藻毒素的所有四种立体异构体的全合成以及在聚酮化合物 C10 和 C11 位置变化的简化类似物。这些化合物对 PANC1 癌细胞系的生物学评估表明，(10R,11S) 构型及其相关的两个取代基对于高效力至关重要。
• Total synthesis and biological evaluation of nannocystin analogues modified at the polyketide phenyl moiety
  作者：Yunfeng Tian、Yahui Ding、Xiaolong Xu、Yanju Bai、Yang Tang、Xin Hao、Weicheng Zhang、Yue Chen

  DOI：10.1016/j.tetlet.2018.07.028

  日期：2018.8

  nannocystin analogues 3a–3j modified at the polyketide phenyl moiety was reported. These compounds were evaluated against three cancer cell lines. Compared with the naturally occurring congener 3a, the other synthetic variants either preserved or lose antiproliferative activity at varying degrees. Moreover, the potent analogues also displayed comparable levels of cytotoxicity toward two normal cell lines

  据报道，在聚酮化合物苯基部分修饰的一组集中的10种纳米囊藻毒素类似物3a – 3j的总合成。针对三种癌细胞系评估了这些化合物。与天然同源物3a相比，其他合成变体在不同程度上保留或丧失了抗增殖活性。而且，有效的类似物对两种正常细胞系也显示出可比较的细胞毒性水平。