[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-9-[3-[6-[6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoylamino]hexanoylamino]propanoyloxy]-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-9-[3-[6-[6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoylamino]hexanoylamino]propanoyloxy]-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• 化学式: C₁₉H₁₈NO₄Pol
• 分子量: 1377.6
• InChiKey: SFIBEHAZJOYNOS-ZOKYLNBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  98
• 可旋转键数：
  36
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  381
• 氢给体数：
  8
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  (L)-2((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-8-oxodecanoic acid 、 Fmoc-(N-iBu)-βAla-OH 、 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-9-[3-[6-[6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoylamino]hexanoylamino]propanoyloxy]-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate 、 Fmoc-L-色氨酸 在 哌啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成
  参考文献：
  名称：

  Macrocyclic Peptoid–Peptide Hybrids as Inhibitors of Class I Histone Deacetylases

  摘要：

  We report the design, synthesis, and biological evaluation of the first macrocyclic peptoid-containing histone deacetylase (HDAC) inhibitors. The compounds selectively inhibit human class I HDAC isoforms in vitro, with no inhibition of the tubulin deacetylase activity associated with class IIb HDAC6 in cultured Jurkat cells. Compared to the natural product apicidin (1), one inhibitor (compound 10) showed equivalent potency against K-562 cells, but was more cytoselective across a panel of cancer cell lines.

  DOI：

  10.1021/ml300162r
• 作为产物：
  描述：

  7-(β-alanyl)paclitaxel 、 联锡酰氨基己酰-6-氨基己酸N-羟基琥珀酰亚胺酯 在 N-乙基吗啉 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以35 mg的产率得到[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-9-[3-[6-[6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoylamino]hexanoylamino]propanoyloxy]-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  具有超长链间隔臂的生物素化紫杉醇的合成与生物学评价

  摘要：

  使用改进的合成反应序列合成了具有超长链（LC-LC-生物素）间隔臂的生物素化紫杉醇衍生物。生物素化的紫杉醇类似物在体外保留了极好的微管稳定活性。此外，该类似物可以同时结合链霉亲和素和微管上的结合位点，使其适用于定位研究或通过链霉亲和素键将紫杉醇连接到固体基质上。

  DOI：

  10.1021/ml300149z

文献信息

• Combinatorial Solid-Phase Synthesis and Biological Evaluation of Cyclodepsipeptide Destruxin B as a Negative Regulator for Osteoclast Morphology
  作者：Hiroshi Sato、Masahito Yoshida、Hayato Murase、Hiroshi Nakagawa、Takayuki Doi

  DOI：10.1021/acscombsci.6b00076

  日期：2016.9.12

  Combinatorial synthesis and biological evaluation of cyclodepsipeptide destruxin B have been achieved. The cyclization precursors were prepared by solid-phase peptide synthesis via a split and pool method utilizing SynPhase lanterns with colored tags and cogs, followed by cleavage from the polymer-support. Macrolactonization utilizing MNBA-DMAPO in solution-phase was successfully performed in parallel to afford

  环二肽destruxin B的组合合成和生物学评估已实现。环化前体是通过固相肽合成，使用具有彩色标签和嵌齿轮的SynPhase提灯，通过分体和合并方法制备的，然后从聚合物载体上裂解下来的。在溶液相中成功并行利用MNBA-DMAPO进行了大环内酯化，以中等至良好的收率提供了所需的64元destruxin类似物。合成类似物的生物学评估表明，构件A的MeAla残基需要诱导破骨细胞样多核细胞（OCL）的所需形态变化，并在R 4处引入取代基 形态可容忍脯氨酸部分的位置，并且可以使破骨细胞中用于靶标识别的分子探针的制备成为可能。
• Macrocyclic Peptoid–Peptide Hybrids as Inhibitors of Class I Histone Deacetylases
  作者：Christian A. Olsen、Ana Montero、Luke J. Leman、M. Reza Ghadiri

  DOI：10.1021/ml300162r

  日期：2012.9.13

  We report the design, synthesis, and biological evaluation of the first macrocyclic peptoid-containing histone deacetylase (HDAC) inhibitors. The compounds selectively inhibit human class I HDAC isoforms in vitro, with no inhibition of the tubulin deacetylase activity associated with class IIb HDAC6 in cultured Jurkat cells. Compared to the natural product apicidin (1), one inhibitor (compound 10) showed equivalent potency against K-562 cells, but was more cytoselective across a panel of cancer cell lines.
• Synthesis and Biological Evaluation of a Biotinylated Paclitaxel with an Extra-Long Chain Spacer Arm
  作者：Lev. G. Lis、Mary A. Smart、Anna Luchniak、Mohan L. Gupta、Vadim J. Gurvich

  DOI：10.1021/ml300149z

  日期：2012.9.13

  A biotinylated paclitaxel derivative with an extra-long chain (LC-LC-biotin) spacer arm was synthesized using an improved synthetic reaction sequence. The biotinylated paclitaxel analogue retained excellent microtubule stabilizing activity in vitro. Furthermore, it was shown that this analogue can simultaneously engage streptavidin and the binding site on microtubules, making it suitable for localization

  使用改进的合成反应序列合成了具有超长链（LC-LC-生物素）间隔臂的生物素化紫杉醇衍生物。生物素化的紫杉醇类似物在体外保留了极好的微管稳定活性。此外，该类似物可以同时结合链霉亲和素和微管上的结合位点，使其适用于定位研究或通过链霉亲和素键将紫杉醇连接到固体基质上。