((2R,3S,Z)-3-amino-9-ethoxy-2-methyl-9-oxonon-5-enoyl)-L-valyl-L-alanyl-L-phenylalanine | 934400-61-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ((2R,3S,Z)-3-amino-9-ethoxy-2-methyl-9-oxonon-5-enoyl)-L-valyl-L-alanyl-L-phenylalanine
• CAS: 934400-61-0
• 化学式: C₂₉H₄₄N₄O₇
• 分子量: 560.691
• InChiKey: OEFRWHQYHSQWQP-XGFSJKMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  40.0
• 可旋转键数：
  17.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  176.92
• 氢给体数：
  5.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ((2R,3S,Z)-3-amino-9-ethoxy-2-methyl-9-oxonon-5-enoyl)-L-valyl-L-alanyl-L-phenylalanine 在 五氟苯基二苯基磷酸酯 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 以18.2 mg的产率得到ethyl (Z)-6-((2S,5S,8S,11S,12R)-8-benzyl-2-isopropyl-5,12-dimethyl-3,6,9,13-tetraoxo-1,4,7,10-tetraazacyclotridecan-11-yl)hex-4-enoate
  参考文献：
  名称：

  Molecular Insights into Azumamide E Histone Deacetylases Inhibitory Activity

  摘要：

  Azumamide E, a cyclotetrapeptide isolated from the sponge Mycale izuensis, is the most powerful carboxylic acid containing natural histone deacetylase (HDAC) inhibitor known to date. In this paper, we describe design and synthesis of two stereochemical variants of the natural product. These compounds have allowed us to clarify the influence of side chain topology on the HDAC-inhibitory activity. The present contribution also reveals the identity of the recognition pattern between azumamides and the histone deacetylase-like protein (HDLP) model receptor and reports the azumamide E unprecedented isoform selectivity on histone deacetylases class subtypes. From the present studies, a plausible model for the interaction of azumamides with the receptor binding pocket is derived, providing a framework for the rational design of new cyclotetrapeptide-based HDAC inhibitors as antitumor agents.

  DOI：

  10.1021/ja0686256
• 作为产物：
  描述：

  L-苯丙氨酸叔丁酯盐酸盐 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 二乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 55.99h， 生成 ((2R,3S,Z)-3-amino-9-ethoxy-2-methyl-9-oxonon-5-enoyl)-L-valyl-L-alanyl-L-phenylalanine
  参考文献：
  名称：

  Molecular Insights into Azumamide E Histone Deacetylases Inhibitory Activity

  摘要：

  Azumamide E, a cyclotetrapeptide isolated from the sponge Mycale izuensis, is the most powerful carboxylic acid containing natural histone deacetylase (HDAC) inhibitor known to date. In this paper, we describe design and synthesis of two stereochemical variants of the natural product. These compounds have allowed us to clarify the influence of side chain topology on the HDAC-inhibitory activity. The present contribution also reveals the identity of the recognition pattern between azumamides and the histone deacetylase-like protein (HDLP) model receptor and reports the azumamide E unprecedented isoform selectivity on histone deacetylases class subtypes. From the present studies, a plausible model for the interaction of azumamides with the receptor binding pocket is derived, providing a framework for the rational design of new cyclotetrapeptide-based HDAC inhibitors as antitumor agents.

  DOI：

  10.1021/ja0686256